Publications by authors named "Wolfram Sterry"

300 Publications

A Contemporary View on Felix Pinkus' Concept of the Vitreous Membrane.

Skin Appendage Disord 2020 Jan 17;6(1):25-31. Epub 2019 Oct 17.

Department of Dermatology and Allergology, Clinical Research Center for Hair and Skin Science, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and -Berlin Institute of Health, Berlin, Germany.

Introduction: Felix Pinkus' concept of the vitreous membrane (VM) published in 1927 describes circular folds protruding into the outer root sheath (ORS), which, in his opinion, serve as interdigitations between the outer root sheath (ORS) and the VM. This concept currently seems to have fallen into oblivion.

Objective: To determine the origin and possible function of the VM in the proliferation and vascularization of the hair follicle (HF).

Methods: Serial investigation of healthy skin probes with histological (hematoxylin & eosin and periodic acid-Schiff) and immunohistochemical examination (Ki67, CD56, CD8, and collagen IV) were performed.

Results: Morphological variations of the VM in various HFs such as protrusions and folds, the latter unilateral, bilateral or circular, some acute-angled, were found. Similarly, protrusions of the VM into the ORS were observed, that consisted of capillary tissue together with perifollicular tissue and VM mimicking minimal variants of the dermal papilla.

Conclusions: Pinkus' concept of the VM is revisited, reproduced and possible functions are proposed. Since these structures are found in a HF region with a high metabolic dynamism, they may be involved in differentiation or nutrition, or else be formed as a result of pressure arising from outgrowing hair shafts.
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http://dx.doi.org/10.1159/000503330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995965PMC
January 2020

Umbruch und Aufbruch Laudatio zum 80. Geburtstag von Dr. Erich Schubert.

J Dtsch Dermatol Ges 2019 Oct;17(10):1105-1107

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http://dx.doi.org/10.1111/ddg.13940_gDOI Listing
October 2019

Fluorescence optical imaging for the detection of potential psoriatic arthritis in comparison to musculoskeletal ultrasound.

J Dtsch Dermatol Ges 2019 Sep;17(9):913-921

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Objective: Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA).

Methods: Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2-5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1-3.

Results: FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI.

Conclusions: The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.
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http://dx.doi.org/10.1111/ddg.13931DOI Listing
September 2019

The IL-1 Pathway Is Hyperactive in Hidradenitis Suppurativa and Contributes to Skin Infiltration and Destruction.

J Invest Dermatol 2019 06 5;139(6):1294-1305. Epub 2018 Dec 5.

Interdisciplinary Group Molecular Immunopathology, Dermatology/Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Psoriasis Research and Treatment Center, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Hidradenitis suppurativa (HS) (also designated acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. When we examined the HS cytokine pattern, IL-1β turned out to be a highly prominent cytokine, overexpressed even compared with psoriatic lesions. Analyses of IL-1β-induced transcriptome in various cell types showed overlapping profiles, with upregulations of molecules causing immune cell infiltration and extracellular matrix degradation, and of specific cytokines including IL-6, IL-32, and IL-36. Matching cellular IL-1 receptor levels, dermal fibroblasts showed both the strongest and broadest IL-1β response, which was not clearly shared or strengthened by other cytokines. The IL-1β signature was specifically present in HS lesions and could be reversed by application of IL-1 receptor antagonist. Search for blood parameters associated with IL-1β pathway activity in HS identified serum amyloid A, which was synergistically induced by IL-1β and IL-6 in hepatocytes. Consequently, strongly elevated blood serum amyloid A levels in HS correlated positively with the extent of inflammatory skin alterations. In summary, the IL-1β pathway represents a pathogenetic cascade, whose activity may be therapeutically targeted and monitored by blood SAA levels.
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http://dx.doi.org/10.1016/j.jid.2018.11.018DOI Listing
June 2019

Association of Hidradenitis Suppurativa With Body Image.

JAMA Dermatol 2018 04;154(4):447-451

Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.

Importance: Hidradenitis suppurativa (HS) leads to disfigurement and painful eruptions in terminal hair follicles of the intertriginous skin, mainly of axillary, genitofemoral, and perianal sites. It is associated with an excessive impairment of quality of life, psychiatric disorders, and sexual distress. Body image impairment has been linked to depression and anxiety and has been described for some dermatologic disorders but has not yet been investigated in patients with HS.

Objectives: To investigate whether body image is diminished in patients with HS and whether disease severity, age at onset, disease duration, obesity, depression, and anxiety are linked to body image impairment.

Design, Setting, And Participants: This 12-month (August 1, 2009, to August 31, 2010) case-control study with a prospective, observational, cross-sectional design recruited 47 consecutive patients with HS entering a tertiary care center and 45 healthy control individuals matched for age, sex, and body mass index (BMI). One patient and 4 controls failed to complete the questionnaire and were excluded from the evaluation. Data analysis was performed from December 1, 2013, to February 15, 2014.

Main Outcomes And Measures: The Frankfurt Body Concept Scale (FKKS) and the Hospital Anxiety and Depression Scale (HADS) were given to patients and controls. Correlations among FKKS, HADS, and disease features were calculated.

Results: Of the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6 [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P < .001), even when controlled for BMI. A correlation was found for the extent of body image disruption and BMI (r = -0.589; P < .001), HADS-depression score (r = -0.619; P < .001), and HADS-anxiety score (r = -0.340; P = .03). No association was found for the body image score and the severity of HS, age at onset of disease, and duration of disease. The body contact subscale score was the only subscale score that was not different between patients with HS and controls.

Conclusions And Relevance: Patients with HS have major body image impairment, which might lead to depression and anxiety, disorders that have been largely acknowledged in HS. This study identified another element of the psychosocial burden of patients with HS and reveals that body image could potentially be used as an outcome measure in future studies of HS.
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http://dx.doi.org/10.1001/jamadermatol.2017.6058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876839PMC
April 2018

IL-32 induces indoleamine 2,3-dioxygenaseCD1c dendritic cells and indoleamine 2,3-dioxygenaseCD163 macrophages: Relevance to mycosis fungoides progression.

Oncoimmunology 2017;6(2):e1181237. Epub 2016 May 5.

Laboratory for Investigative Dermatology, The Rockefeller University , New York, NY, USA.

Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c myeloid dendritic cells (mDC) and/or CD163 macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes. DCs matured by IL-32 had the phenotype of skin-resident DCs (CD1c), but more importantly, also had high expression of indoleamine 2,3-dioxygenase. The presence of DCs with these markers was demonstrated in MF skin lesions. At a molecular level, indoleamine 2,3-dioxygenase messenger RNA (mRNA) levels in MF lesions were higher than those in healthy volunteers, and there was a high correlation between indoleamine 2,3-dioxygenase and IL-32 expression. In contrast, Foxp3 mRNA levels decreased from patch to tumor stage. Increasing expression of IL-10 across MF lesions was highly correlated with IL-32 and indoleamine 2,3-dioxygenase, but not with Foxp3 expression. Thus, IL-32 could contribute to progressive immune dysregulation in MF by directly fostering development of immunosuppressive mDC or macrophages, possibly in association with IL-10.
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http://dx.doi.org/10.1080/2162402X.2016.1181237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353917PMC
May 2016

MMP8 Is Increased in Lesions and Blood of Acne Inversa Patients: A Potential Link to Skin Destruction and Metabolic Alterations.

Mediators Inflamm 2016 23;2016:4097574. Epub 2016 Oct 23.

Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Research Center Immunosciences, University Hospital Charité, Berlin, Germany.

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF- stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF- blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment.
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http://dx.doi.org/10.1155/2016/4097574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097814PMC
August 2017

Inactivation of RUNX3/p46 Promotes Cutaneous T-Cell Lymphoma.

J Invest Dermatol 2016 11 1;136(11):2287-2296. Epub 2016 Jul 1.

Department of Dermatology, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Institute of Pathology, Charité - Universitaetsmedizin Berlin, Berlin, Germany. Electronic address:

The key role of RUNX3 in physiological T-cell differentiation has been extensively documented. However, information on its relevance for the development of human T-cell lymphomas or leukemias is scarce. Here, we show that alterations of RUNX3 by either heterozygous deletion or methylation of its distal promoter can be observed in the tumor cells of 15 of 21 (71%) patients suffering from Sézary syndrome, an aggressive variant of cutaneous T-cell lymphoma. As a consequence, mRNA levels of RUNX3/p46, the isoform controlled by the distal promoter, are significantly lower in Sézary syndrome tumor cells. Re-expression of RUNX3/p46 reduces cell viability and promotes apoptosis in a RUNX3/p46 cell line of cutaneous T-cell lymphoma. Based on this, we present evidence that RUNX3 can act as a tumor suppressor in a human T-cell malignancy and suggest that this effect is predominantly mediated through transcripts from its distal promoter, in particular RUNX3/p46.
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http://dx.doi.org/10.1016/j.jid.2016.05.126DOI Listing
November 2016

Age-Associated Skin Conditions and Diseases: Current Perspectives and Future Options.

Gerontologist 2016 Apr;56 Suppl 2:S230-42

The Dermatology Centre, University of Manchester, Academic Health Science Centre, UK. The International League of Dermatological Societies, London, UK.

The International League of Dermatological Societies (ILDS), a global, not-for-profit organization representing 157 dermatological societies worldwide, has identified the consequences of skin aging as one of the most important grand challenges in global skin health. Reduced functional capacity and increased susceptibility of the skin with development of dermatoses such as dry skin, itching, ulcers, dyspigmentation, wrinkles, fungal infections, as well as benign and malignant tumors are the most common skin conditions in aged populations worldwide. Environmental (e.g., pollution) and lifestyle factors (e.g., smoking, sunbed use) negatively affect skin health. In turn altered appearance, dry skin, chronic wounds, and other conditions decrease general health and reduce the likelihood for healthy and active aging. Preventive skin care includes primary, secondary, and tertiary interventions. Continuous sun protection from early childhood onward is most important, to avoid extrinsic skin damage and skin cancer. Exposure to irritants, allergens, or other molecules damaging the skin must be avoided or reduced to a minimum. Public health approaches are needed to implement preventive and basic skin care worldwide to reach high numbers of dermatological patients and care receivers. Education of primary caregivers and implementation of community dermatology are successful strategies in resource-poor countries. Besides specialist physicians, nurses and other health care professionals play important roles in preventing and managing age-related skin conditions in developing as well as in developed countries. Healthy skin across the life course leads to better mental and emotional health, positive impact on social engagement, and healthier, more active, and productive lives.
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http://dx.doi.org/10.1093/geront/gnw003DOI Listing
April 2016

Influence of Topical, Systemic and Combined Application of Antioxidants on the Barrier Properties of the Human Skin.

Skin Pharmacol Physiol 2016 23;29(1):41-6. Epub 2016 Jan 23.

Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charitx00E9; - Universitx00E4;tsmedizin Berlin, Berlin, Germany.

Background: The formation of free radicals in human skin by solar ultraviolet radiation is considered to be the main reason for extrinsic skin aging. The antioxidants in human tissue represent an efficient protection system against the destructive action of these reactive free radicals. In this study, the parameters of the skin, epidermal thickness, stratum corneum moisture, elasticity and wrinkle volume, were determined before and after the treatment with antioxidant- or placebo-containing tablets and creams.

Methods: The study included 5 groups of 15 volunteers each, who were treated for 2 months with antioxidant-containing or placebo tablets, creams or a combination of antioxidant-containing tablets and cream. The skin parameters were measured at time point 0 and at week 8 utilizing ultrasound for the determination of epidermal thickness, a corneometer for stratum corneum moisture measurements, skin profilometry for quantifying the wrinkle volume and a cutometer for determining the elasticity.

Results: The verum cream had a positive influence on epidermal thickness, elasticity and skin moisture, but the verum tablets improved the epidermal thickness only. The combined application of verum tablets and creams led to a significant improvement of all investigated skin parameters, whereas the application of placebo tablets or cream did not influence any parameters.

Conclusion: The topical and oral supplementation of antioxidants can be an instrument to improve several skin parameters and potentially counteract or decelerate the process of extrinsic skin aging.
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http://dx.doi.org/10.1159/000441953DOI Listing
November 2016

Large molecular systems landscape uncovers T cell trapping in human skin cancer.

Sci Rep 2016 Jan 13;6:19012. Epub 2016 Jan 13.

Molecular Pattern Recognition Research Group, Medical Faculty, OvG University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany.

Immune surveillance of tumour cells is an important function of CD8 T lymphocytes, which has failed in cancer for reasons still unknown in many respect but mainly related to cellular processes in the tumour microenvironment. Applying imaging cycler microscopy to analyse the immune contexture in a human skin cancer we could identify and map 7,000 distinct cell surface-associated multi-protein assemblies. The resulting combinatorial geometry-based high-functional resolution led to discovery of a mechanism of T cell trapping in the epidermis, which involves SPIKE, a network of suprabasal keratinocyte projections piercing and interconnecting CD8 T cells. It appears initiated by clusters of infrabasal T and dendritic cells connected via cell projections across a fractured basal lamina to suprabasal keratinocytes and T lymphocytes.
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http://dx.doi.org/10.1038/srep19012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725819PMC
January 2016

[Not Available].

Authors:
Wolfram Sterry

J Dtsch Dermatol Ges 2015 Dec;13(12):1312

Berlin.

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http://dx.doi.org/10.1111/ddg.12873DOI Listing
December 2015

Interleukin-29 induces epithelial production of CXCR3A ligands and T-cell infiltration.

J Mol Med (Berl) 2016 Apr 26;94(4):391-400. Epub 2015 Nov 26.

Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany.

Unlabelled: Psoriasis is considered as a model for chronic immune-mediated disorders. Th17-cells are pivotal players in those diseases. Recently, we demonstrated that Th17-cells produce interleukin (IL)-29 and that IL-29 is highly present in psoriatic lesions. Whether IL-29, with its action on epithelial cells and melanocytes, contributes to psoriasis pathogenesis, was unknown so far. Analysis of IL-29-treated human keratinocytes revealed induction of the chemokines CXCL10, CXCL11, and, to a much lesser extent, CXCL9. Unlike these CXCR3A ligands, known to attract Th1-, CD8(+), NK-, and Th1/Th17 transient cells, no influence was found on chemokines attracting other immune cell populations or on molecules modulating the CXCR3A/CXCR3A ligand interaction. CXCR3A ligand expression was also induced by IL-29 in melanocytes and in epidermis models and explanted skin. Regarding other psoriasis-relevant cytokines, interferon-γ and, less potently, tumor necrosis factor-α and IL-1β shared and strengthened IL-29's capacity. Murine IL-29 counterpart injected into mouse skin provoked local CXCL10 and CXCL11 expression, T-cell infiltration, and, in consequence, skin swelling. The elevated IL-29 expression in psoriatic lesions was associated with upregulation of CXCR3A ligands compared to non-lesional skin of these patients and to the skin of healthy donors and atopic dermatitis patients, which lack IL-29 production. Importantly, neutralization of IL-29 reduced CXCR3A ligand levels in explant cultures of psoriatic lesions. Finally, elevated blood CXCL11 levels were found in psoriasis that might be useful for monitoring lesional activity of the IL-29 axis. In summary, the Th17-cytokine IL-29 induces specific chemokines and, in consequence, provokes skin infiltration of potentially pathogenic T-cells.

Key Messages: IL-29 selectively induces CXCR3A-binding chemokines (CXCL9, CXCL10, CXCL11) in skin cells. Murine IL-29 counterpart induces skin T-cell infiltration and inflammation in mice. CXCR3A ligands are IL-29-dependently increased in lesional skin of psoriasis patients. CXCR3A ligand levels in psoriatic skin correlate with epidermal T-cell numbers. Increased blood CXCL11 levels in psoriasis may be a biomarker for local IL-29 action.
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http://dx.doi.org/10.1007/s00109-015-1367-yDOI Listing
April 2016

[Obituary for Walter Burgdorf, the longtime co-editor of JDDG].

Authors:
Wolfram Sterry

J Dtsch Dermatol Ges 2015 Aug;13(8):739-40

Berlin.

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http://dx.doi.org/10.1111/ddg.12770DOI Listing
August 2015

Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target.

J Invest Dermatol 2015 Sep 7;135(9):2292-2300. Epub 2015 Apr 7.

Department of Dermatology and Allergy, Skin Cancer Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany; HELIOS Klinikum Krefeld, Krefeld, Germany. Electronic address:

Cutaneous T-cell lymphomas (CTCLs) form a heterogeneous group of non-Hodgkin's lymphomas characterized by only poor prognosis in advanced stage. Despite significant progress made in the identification of novel genes and pathways involved in the pathogenesis of cutaneous lymphoma, the therapeutic value of these findings has still to be proven. Here, we demonstrate by gene expression arrays that Aurora kinase A is one of the highly overexpressed genes of the serine/threonine kinase in CTCL. The finding was confirmed by quantitative reverse transcriptase-PCR, western blotting, and immunohistochemistry in CTCL cell lines and primary patient samples. Moreover, treatment with a specific Aurora kinase A inhibitor blocks cell proliferation by inducing cell cycle arrest in G2 phase, as well as apoptosis in CTCL cell lines. These data provide a promising rationale for using Aurora kinase A inhibition as a therapeutic modality of CTCL.
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http://dx.doi.org/10.1038/jid.2015.139DOI Listing
September 2015

[The official publications of DDG: The history of JDDG].

Authors:
Wolfram Sterry

J Dtsch Dermatol Ges 2014 Nov;12 Suppl 4:32

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http://dx.doi.org/10.1111/ddg.12481DOI Listing
November 2014

Global unity in action at the World Congress of Dermatology--Vancouver 2015.

J Invest Dermatol 2014 Oct;134(10):2477-2479

23rd World Congress of Dermatology and the International League of Dermatological Societies.

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http://dx.doi.org/10.1038/jid.2014.314DOI Listing
October 2014

Deficient cutaneous antibacterial competence in cutaneous T-cell lymphomas: role of Th2-mediated biased Th17 function.

Clin Cancer Res 2014 Nov 11;20(21):5507-16. Epub 2014 Sep 11.

Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany. Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany. Research Center Immunosciences, University Hospital Charité, Berlin, Germany.

Purpose: Primary cutaneous T-cell lymphomas (CTCL) are neoplastic disorders of skin-homing T cells. Affected skin areas show morphologic similarities with alterations in other T-cell-mediated dermatoses. Furthermore, as in atopic dermatitis but in contrast with psoriasis, patients with CTCL are frequently afflicted by cutaneous bacterial infections that support the survival of lymphoma cells. Our aim was to investigate the mechanisms of elevated susceptibility to cutaneous infections in patients with CTCL.

Experimental Design: Skin samples from CTCL, psoriasis, and atopic dermatitis patients were used to illuminate the antibacterial competence status and the presence of its modulating cytokines. For substantiation of findings, 3-dimensional epidermis models, isolated and in vitro generated Th-subpopulations, were applied. Parameters were analyzed via qPCR and IHC.

Results: CTCL lesions compared with psoriatic lesions presented an impaired upregulation of antibacterial proteins (ABPs), with levels even below those in atopic dermatitis. This was associated with a relative deficiency of the ABP-inducing cytokine IL-17 and a strong presence of the ABP-downregulating cytokine IL-13. The simultaneous presence of the Th17-cell cytokine IL-26 indicated that IL-17 deficiency in CTCL lesions results from functional deviation of Th17 cells. Accordingly, IL-17 but not IL-26 production by Th17 cells in vitro was inhibited by IL-4Rα ligand. Levels of other ABP inducers were comparable between CTCL and psoriasis lesions. The same was true about IL-22/TNF-α targets, including the keratinocyte hyper-regeneration marker K16 and the matrix-degrading enzyme MMP1.

Conclusion: Our results suggest that the cutaneous bacterial infections in CTCL are caused by impaired ABP induction as consequence of Th2-mediated biased Th17-cell function.
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http://dx.doi.org/10.1158/1078-0432.CCR-14-0707DOI Listing
November 2014

IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis.

J Invest Dermatol 2014 Nov 21;134(11):2757-2767. Epub 2014 Jul 21.

Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany; Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany; Research Center Immunosciences, University Hospital Charité, Berlin, Germany. Electronic address:

Psoriasis is a common chronic inflammatory disease with characteristic skin alterations and functions as a model of immune-mediated disorders. Cytokines have a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30 individually quantified cytokines, IL-19 showed the strongest differential expression between psoriatic lesions and healthy skin. Cutaneous IL-19 overproduction was reflected by elevated IL-19 blood levels that correlated with psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced both cutaneous and systemic IL-19 levels. IL-19 production was induced in keratinocytes by IL-17A and was further amplified by tumor necrosis factor-α and IL-22. Among skin cells, keratinocytes were found to be important targets of IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1β, IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had no clear influence on the differentiation, proliferation, or migration of these cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes, including the induction of β-defensins, IL-19, IL-23p19, and T helper type 17-cell- and neutrophil-attracting chemokines. In summary, IL-19 as a component of the IL-23/IL-17 axis strengthens the IL-17A action and might be a biomarker for the activity of this axis in chronic inflammatory disorders.
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http://dx.doi.org/10.1038/jid.2014.308DOI Listing
November 2014

Antioxidants in Asian-Korean and caucasian skin: the influence of nutrition and stress.

Skin Pharmacol Physiol 2014 26;27(6):293-302. Epub 2014 Jun 26.

Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: The antioxidant status of the human skin provides protection against the destructive action of free radicals. Most antioxidants cannot be synthesized by the human organism itself, but have to be ingested with a healthy nutrition rich in fruit and vegetables. The Korean cuisine is known to be one of the healthiest worldwide. This binational study investigated the cutaneous carotenoid concentrations in German subjects, South Korean subjects and immigrant Korean subjects resident in Germany and examined whether dietary- and lifestyle-related differences are reflected in the cutaneous carotenoid concentrations.

Methods: Measurements of the carotenoid concentrations of 714 healthy volunteers were performed using a non-invasive spectroscopic measurement system based on reflectance spectroscopy.

Results: In the present study South Korean residents showed a significantly higher antioxidant status than both native German residents and Korean immigrants living in Germany (p < 0.001). The first generation of Korean immigrants to Germany over the age of 50 mostly preserved Korean dietary habits, showing significantly higher concentrations (p < 0.001) than the German-born second and third Korean generations under the age of 50.

Conclusion: The results of the study indicate that a healthy nutrition alone does not provide a high antioxidant status unless the stress exposure can be reduced simultaneously.
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http://dx.doi.org/10.1159/000361053DOI Listing
March 2015

IL32 is progressively expressed in mycosis fungoides independent of helper T-cell 2 and helper T-cell 9 polarization.

Cancer Immunol Res 2014 Sep 17;2(9):890-900. Epub 2014 Jun 17.

Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.

Mycosis fungoides, the most common type of cutaneous T-cell lymphoma (CTCL), is characterized by a helper T-cell 2 (Th2) skewing with a mature CD4(+) memory T-cell phenotype. Using skin samples from patients with mycosis fungoides (n = 21), healthy volunteers (n = 17), and individuals with atopic dermatitis (n = 17) and psoriasis (n = 9), we found IL32 mRNA expression significantly higher in mycosis fungoides samples than in samples from benign inflammatory skin diseases, and its expression increases with disease progression. By IHC and immunofluorescence, we confirmed IL32 protein expression in many CD3(+)CD4(+) T cells and some epidermotropic T cells in mycosis fungoides lesions. MyLa cells (a mycosis fungoides cell line) express IL32, which, in turn, could promote cellular proliferation and viability in a dose-dependent fashion. IL32-treated MyLa and CTCL HH cells upregulated cell proliferation and survival genes. Of the major "polarizing" T-cell cytokines, only IFNγ mRNA increases with mycosis fungoides progression and positively correlates with IL32 mRNA expression. Th2 cytokines do not positively correlate with IL32 mRNA expression or mycosis fungoides progression. Furthermore, by flow cytometry, IL32 production by circulating activated T cells in healthy individuals was found in both IFNγ(+) and IFNγ(-) cells but not in IL4(+) or IL13(+) cells. In conclusion, we have identified IL32(+) cells as the likely tumor cells in mycosis fungoides, and demonstrated that IL32 mRNA expression increases with mycosis fungoides progression and is significantly higher than mRNA expression in other skin diseases, and that some IL32(+) T cells are independent from the defined Th subsets. Thus, IL32 may play a unique role in mycosis fungoides progression as an autocrine cytokine.
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http://dx.doi.org/10.1158/2326-6066.CIR-13-0199-TDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346156PMC
September 2014

T-cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T-cell lymphomas with the Biomed-2 PCR reveals transient T-cell clones in addition to the tumor clone.

Exp Dermatol 2014 Jul;23(7):504-8

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Detection of a dominant T-cell clone by T-cell receptor (TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T-cell lymphomas (CTCL). The occurrence of T-cell clones in addition to the diagnostic T-cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed-2 PCR for the TCRγ and TCRβ locus. A dominant T-cell clone was repetitively detected in 93% (26/28) of patients. Additional T-cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T-cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T-cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T-cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T-cell clones into account for diagnostic analyses.
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http://dx.doi.org/10.1111/exd.12453DOI Listing
July 2014

Palmoplantar erythrodysesthesia-like skin symptoms in patients under various chemotherapeutics: preventive and therapeutic options.

Skin Pharmacol Physiol 2014 1;27(5):229-33. Epub 2014 May 1.

Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background/aims: The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients.

Methods: 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment.

Results: At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued.

Conclusion: The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation.
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http://dx.doi.org/10.1159/000356780DOI Listing
March 2015

Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop.

Histopathology 2015 Oct 24;67(4):425-41. Epub 2015 Feb 24.

Department of Dermatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico and Università degli Studi di Milano-Bicocca, Milan, Italy.

Aims: Aggressive epidermotropic cutaneous CD8(+) lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8(+) lymphomas.

Methods And Results: Sixty-one CD8(+) cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed and recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8(+) lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and histologically have striking pagetoid epidermotrophism. A CD8(+) /CD45RA(+) /CD45RO(-) /CD2(-) /CD5(-) /CD56(-) phenotype, with one or more cytotoxic markers, was found in seven of 18 patients, with a very similar phenotype in the remainder. The tumours seldom involve lymph nodes, but mucosal and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8(+) mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp disease presented the typical features well documented in the CD4(+) forms of those diseases.

Conclusions: Aggressive epidermotropic cutaneous CD8(+) lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications.
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http://dx.doi.org/10.1111/his.12371DOI Listing
October 2015

IL-29 is produced by T(H)17 cells and mediates the cutaneous antiviral competence in psoriasis.

Sci Transl Med 2013 Sep;5(204):204ra129

Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, 10117 Berlin, Germany.

Psoriasis and atopic dermatitis (AD) are the most common chronic inflammatory skin diseases. Although both patient groups show strongly impaired skin barrier function, only AD patients frequently suffer from cutaneous viral infections. The mechanisms underlying the distinct susceptibilities to these pathogenetic and often life-threatening infections are unknown. We show that antiviral proteins (AVPs) such as MX1, BST2, ISG15, and OAS2 were strongly elevated in psoriatic compared to AD lesions and healthy skin. Of 30 individually quantified cytokines in psoriatic lesions, interleukin-29 (IL-29) was the only mediator whose expression correlated with the AVP levels. IL-29 was absent in AD lesions, and neutralization of IL-29 in psoriatic skin reduced AVP expression. Accordingly, IL-29 raised AVP levels in isolated keratinocytes, epidermis models, and human skin explants, but did not influence antibacterial protein production. AVP induction correlated with increased antiviral defense of IL-29-treated keratinocytes. Furthermore, IL-29 elevated the expression of signaling elements, resulting in increased sensitivity of keratinocytes toward its own action. We identified T helper 17 (T(H)17) cells as IL-29 producers and demonstrated their ability to increase the antiviral competence of keratinocytes in an IL-29-dependent manner. Transforming growth factor-β and the activity of RORγt/RORα were most critical for the development of IL-29-producing T(H)17 cells. IL-29 secretion by these cells was dependent on NFAT and c-Jun N-terminal kinase and was inhibited by IL-4. These data suggest that T(H)17 cell-derived IL-29, which is absent in AD, mediates the robust antiviral state on psoriatic skin, and demonstrate a new function of T(H)17 cells.
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http://dx.doi.org/10.1126/scitranslmed.3006245DOI Listing
September 2013

Efficient prevention strategy against the development of a palmar-plantar erythrodysesthesia during chemotherapy.

Skin Pharmacol Physiol 2014 21;27(2):66-70. Epub 2013 Aug 21.

Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: Pegylated liposomal doxorubicin (PLD) is a highly efficient chemotherapeutic; however, it induces dermal side effects such as palmar-plantar erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with the sweat onto the skin surface.

Aim: The aim of the present study was to examine whether a topically applied ointment containing antioxidants with a high radical protection factor is able to prevent the formation of PPE.

Methods: Twenty patients suffering from ovarian carcinoma and treated with PLD were observed.

Results: 60% of the patients tolerated the regular application of the cream and developed no PPE. The remaining 40% interrupted the application. Six of them developed PPE and resumed ointment application thereafter. In these cases the PPE disappeared or was strongly reduced.

Conclusion: The results of the observation clearly demonstrate that topical application of the ointment is an efficient strategy against the development of PPE during chemotherapy with PLD.
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http://dx.doi.org/10.1159/000351801DOI Listing
September 2014

[Prospects for young academics and clinicians in dermatology].

Authors:
Wolfram Sterry

J Dtsch Dermatol Ges 2013 Sep;11(9):793-4

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http://dx.doi.org/10.1111/ddg.12184DOI Listing
September 2013

Comparative study of hair follicle morphology in eight mammalian species and humans.

Skin Res Technol 2014 May 25;20(2):147-54. Epub 2013 Jun 25.

Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.

Background: The objective of the present study was the investigation of hair follicle morphology in eight mammalian species in order to evaluate the species-specific contribution of hair follicles to skin penetration particularly with regard to the utilization of the different animal species as skin models for human skin.

Methods: Cyanoacrylate skin surface biopsy method (CSSB), light microscopy and also digital photography were used for the measurements of hair follicle morphology.

Results: The results revealed species-specific differences regarding the pattern of hair follicle distribution and also differences with regard to hair follicle parameters and characteristics. The results also showed that hair follicles generally possess enormous reservoir capacities, regarding the follicular volume. In all examined species, hair follicles reached at least one-fifth of stratum corneum storage capacity. The results were compared with human data obtained in a previous study.

Conclusion: With regard to hair follicle morphology and skin structure, the porcine skin seems to be the most appropriate skin model for human skin analog to previous investigations, whereas the skin of dog, cat, and rabbit showed the most significant differences.
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http://dx.doi.org/10.1111/srt.12098DOI Listing
May 2014

Evaluation of optical coherence tomography as a non-invasive diagnostic tool in cutaneous wound healing.

Skin Res Technol 2014 Feb 19;20(1):1-7. Epub 2013 Jun 19.

Department of Dermatology, Venerology and Allergology, Center of Experimental and Applied Cutaneous Physiology (CCP), Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing.

Methods: Optical coherence tomography (OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks.

Results: Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization.

Conclusion: Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time.
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http://dx.doi.org/10.1111/srt.12077DOI Listing
February 2014