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    1 OF 105

    Potential of EPR spin-trapping to investigate in situ free radicals generation from skin allergens in reconstructed human epidermis: cumene hydroperoxide as proof of concept.
    Free Radic Res 2018 Jan 15:1-9. Epub 2018 Jan 15.
    a Dermatochemistry Laboratory , University of Strasbourg, CNRS UMR 7177, Institut le Bel , Strasbourg , France.
    The first step in the development of skin sensitisation to a chemical, and in the elicitation of further allergic contact dermatitis (ACD), is the binding of the allergen to skin proteins after penetrating into the epidermis. The so-formed antigenic adduct is then recognised by the immune system as foreign to the body. Sensitising organic hydroperoxides derived from autoxidation of natural terpenes are believed to form antigens through radical-mediated mechanisms, although this has not yet been established. Read More

    MicroRNA-21-Mediated Inhibition of Mast Cell Degranulation Involved in the Protective Effect of Berberine on 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats via p38 Pathway.
    Inflammation 2017 Dec 27. Epub 2017 Dec 27.
    Department of Pathogen Biology, College of Basic Medicine, Hubei University of Chinese Medicine, No. 1 Huangjiahu West Road, Hongshan District, Wuhan, 430065, China.
    The study aimed to investigate the effect of berberine on allergic contact dermatitis (ACD) in rats and explore its underlying mechanisms. Firstly, ACD model was established by sensitizing and challenging with 2,4-dinitrofluorobenzene (DNFB) topically, and the rats were treated with berberine. Ear swelling was assessed, and cytokine, IgE, and histamine productions were measured. Read More

    Determination of Protein Haptenation by Chemical Sensitisers within the Complexity of the Human Skin Proteome.
    Toxicol Sci 2017 Dec 18. Epub 2017 Dec 18.
    Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.
    Skin sensitisation associated with the development of allergic contact dermatitis (ACD) occurs via a number of specific key events at the cellular level. The molecular initiating event (MIE), the first in the sequence of these events, occurs after exposure of the skin to an electrophilic chemical, causing the irreversible haptenation of proteins within skin. Characterisation of this MIE is a key step in elucidating the skin sensitisation adverse outcome pathway and is essential to providing parameters for mathematical models to predict the capacity of a chemical to cause sensitisation. Read More

    Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of RIPK1 inhibitor GSK2982772 in healthy volunteers.
    Pharmacol Res Perspect 2017 Dec;5(6)
    GlaxoSmithKline, Collegeville, PA, USA.
    GSK2982772 is a highly selective inhibitor of receptor-interacting protein kinase 1 (RIPK1) being developed to treat chronic inflammatory diseases. This first-in-human study evaluated safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of GSK2982772 administered orally to healthy male volunteers. This was a Phase I, randomized, placebo-controlled, double-blind study. Read More

    Phosphodiesterase 4B plays a role in benzophenone-3-induced phototoxicity in normal human keratinocytes.
    Toxicol Appl Pharmacol 2018 Jan 26;338:174-181. Epub 2017 Nov 26.
    College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:
    Benzophenone-3 (BP-3), which is extensively used in organic sunscreen, has phototoxic potential in human skin. Phosphodiesterase 4B (PDE4B) has a well-established role in inflammatory responses in immune cells. Currently, it is unknown if PDE4B is associated with BP-3-induced phototoxicity in normal human keratinocytes (NHKs). Read More

    MCP-1 produced by keratinocytes is associated with leucocyte recruitment during elicitation of nickel-induced occupational allergic contact dermatitis.
    Toxicol Ind Health 2018 Jan 13;34(1):36-43. Epub 2017 Nov 13.
    4 Department of Medical Quality Control, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.
    To investigate the expression profile of monocyte chemoattractant peptide-1 (MCP-1) by keratinocytes after nickel exposure and to identify its role for leucocyte migration during nickel-induced occupational allergic contact dermatitis (OACD), 26 workers diagnosed with nickel-induced OACD were enrolled. Skin biopsies from the positive nickel-challenged sites at different time points were assessed by immunohistochemistry (IHC) for MCP-1, CD68, CD45RO, and in situ hybridization (ISH) for MCP-1, using chronic periumbilical dermititis as controls. The expressions of MCP-1 in HaCaT cell culture after nickel treatment were quantified by enzyme-linked immunosorbent assay. Read More

    Pathomechanisms of Contact Sensitization.
    Curr Allergy Asthma Rep 2017 Nov 11;17(12):83. Epub 2017 Nov 11.
    Allergy Research Group, Department of Dermatology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 7, 79104, Freiburg im Breisgau, Germany.
    Contact sensitization is the initial process involved in the development of an allergic reaction to xenobiotic environmental substances. Here, we briefly describe the differences between irritant and allergic contact dermatitis. Then, we highlight the essential steps involved in the development of an ACD reaction, i. Read More

    Sequencing and De Novo Assembly of the Toxicodendron radicans (Poison Ivy) Transcriptome.
    Genes (Basel) 2017 Nov 10;8(11). Epub 2017 Nov 10.
    Department of Plant Pathology, Physiology, and Weed Science, Virginia Tech, Blacksburg, VA 24061, USA.
    Contact with poison ivy plants is widely dreaded because they produce a natural product called urushiol that is responsible for allergenic contact delayed-dermatitis symptoms lasting for weeks. For this reason, the catchphrase most associated with poison ivy is "leaves of three, let it be", which serves the purpose of both identification and an appeal for avoidance. Ironically, despite this notoriety, there is a dearth of specific knowledge about nearly all other aspects of poison ivy physiology and ecology. Read More

    Mast cells acquire MHCII from dendritic cells during skin inflammation.
    J Exp Med 2017 Dec 30;214(12):3791-3811. Epub 2017 Oct 30.
    Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
    Mast cells (MCs) and dendritic cells (DCs) are essential innate sentinels populating host-environment interfaces. Using longitudinal intravital multiphoton microscopy of DCGFP/MCRFP reporter mice, we herein provide in vivo evidence that migratory DCs execute targeted cell-to-cell interactions with stationary MCs before leaving the inflamed skin to draining lymph nodes. During initial stages of skin inflammation, DCs dynamically scan MCs, whereas at a later stage, long-lasting interactions predominate. Read More

    Editor's Highlight: Fragrance Allergens Linalool and Limonene Allylic Hydroperoxides in Skin Allergy: Mechanisms of Action Focusing on Transcription Factor Nrf2.
    Toxicol Sci 2018 Jan;161(1):139-148
    UMR996 - Inflammation, Chemokines and Immunopathology, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
    Allergic contact dermatitis is regarded as the most frequent expression of immunotoxicity in humans. Many odorant terpenes commonly used in fragrance compositions are considered as weak skin sensitizers, whereas some of their autoxidation products, allylic hydroperoxides, are classified as strong sensitizers according to the local lymph node assay. However, the mechanism of their effects on the immune system remains unclear. Read More

    Proteome Analysis of Urticating Setae From Thaumetopoea pityocampa (Lepidoptera: Notodontidae).
    J Med Entomol 2017 Nov;54(6):1560-1566
    Department of Agronomy Food Natural Resources Animals and Environment (DAFNAE), University of Padova, Viale dell'Universita 16, 35020 Legnaro, Padova, Italy.
    Thaumetopoea pityocampa (Denis & Schiffermüller) (Lepidoptera: Notodontidae) is harmful to conifer trees because of defoliation and to public health because of the release of urticating setae from the caterpillars. Contact with setae by humans and domestic animals induces dermatitis, usually localized to the exposed areas. Recent studies demonstrated the presence of a complex urticating mechanism where proteins present in the setae may play a role as activators of immune responses. Read More

    The Cooperative Role of CD326+ and CD11b+ Dendritic Cell Subsets for a Hapten-Induced Th2 Differentiation.
    J Immunol 2017 Nov 2;199(9):3137-3146. Epub 2017 Oct 2.
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
    Dendritic cells (DCs) play a critical role in directing immune responses. Previous studies have identified a variety of DC subsets and elucidated their context-dependent functions that parallel those of effector Th cell subsets. However, little is known about the DC subsets responsible for differentiation of Th2 cells governing allergic contact dermatitis. Read More

    Lymphangiogenesis Facilitates Initial Lymph Formation and Enhances the Dendritic Cell Mobilizing Chemokine CCL21 Without Affecting Migration.
    Arterioscler Thromb Vasc Biol 2017 Nov 21;37(11):2128-2135. Epub 2017 Sep 21.
    From the Department of Biomedicine, University of Bergen, Norway (T.V.K., T.R., A.T., E.N., T.S., M.W., O.T., H.W.); and Departments of Medicine (E.N.) and Pathology (M.W.), Haukeland University Hospital, Bergen, Norway.
    Objective: Lymphatic vessels play an important role in body fluid, as well as immune system homeostasis. Although the role of malfunctioning or missing lymphatics has been studied extensively, less is known on the functional consequences of a chronically expanded lymphatic network or lymphangiogenesis.

    Approach And Results: To this end, we used K14-VEGF-C (keratin-14 vascular endothelial growth factor-C) transgenic mice overexpressing the vascular endothelial growth factor C in skin and investigated the responses to inflammatory and fluid volume challenges. Read More

    Effects of Acupuncture on 1-chloro-2,4-dinitrochlorobenzene-induced Allergic Contact Dermatitis in Mice.
    J Acupunct Meridian Stud 2017 Aug 11;10(4):252-260. Epub 2017 Jul 11.
    Shandong Medicine Technician College, Tai'an, Shandong, China. Electronic address:
    Allergic contact dermatitis (ACD) is a chronic inflammatory skin disease. Topical corticosteroids are the first-line therapy for ACD despite their significant adverse effects. Acupuncture has been widely used in the treatment of various skin diseases, but its underlying mechanism remains unrevealed. Read More

    Caspase inhibitors: a review of recently patented compounds (2013-2015).
    Expert Opin Ther Pat 2018 Jan 18;28(1):47-59. Epub 2017 Sep 18.
    a Cancer Molecular Targeted Herbal Research Center, College of Korean Medicine , Kyung Hee University , Seoul , South Korea.
    Introduction: Although many caspase inhibitors have been patented, caspase inhibitors have not entered the market due to their toxicity and poor pharmacokinetic profile. Areas covered: In this article, we review patents (2013-2015) for peptide and non-peptide caspase inhibitors and their compositions. Expert opinion: Noteworthy patents include a peptidic caspase-2 inhibitor for nasal administration and a peptidomimetic caspase-6 inhibitor that can be administered via several routes for the treatment of neurodegenerative diseases. Read More

    Prediction of skin sensitization potency sub-categories using peptide reactivity data.
    Toxicol In Vitro 2017 Dec 4;45(Pt 1):134-145. Epub 2017 Sep 4.
    BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany. Electronic address:
    While the skin sensitization hazard of substances can already be identified using non-animal methods, the classification of potency sub-categories GHS-1A and 1B is still challenging. Potency can be measured by the dose at which an effect is observed; since the protein-adduct formation is determining the dose of the allergen in the skin, peptide reactivity was used to assess the potency. The Direct Peptide Reactivity Assay (DPRA; one concentration and reaction-time) did not sufficiently discriminate between sub-categories 1A and 1B (56% accuracy compared to LLNA data, n=124). Read More

    Polymorphic light eruption and IL-1 family members: any difference with allergic contact dermatitis?
    Photochem Photobiol Sci 2017 Sep;16(9):1471-1479
    Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana" University of Salerno, Italy.
    Polymorphic light eruption (PLE) is described as a delayed-type hypersensitivity reaction (DTHR) toward a de novo light-induced antigen, yet to be identified. In effect, the inflammatory pathways of PLE and allergic contact dermatitis (ACD) share common patterns in terms of the mediators involved from the innate and adaptive immune system participating in the DTHR. As we have previously highlighted the role of interleukin (IL)-1 family members in ACD, we hypothesised that the same mediators could have similar functions in PLE. Read More

    Occupational contact urticaria and protein contact dermatitis: causes and concomitant airway diseases.
    Contact Dermatitis 2017 Dec 10;77(6):390-396. Epub 2017 Aug 10.
    Occupational Medicine, Finnish Institute of Occupational Health, 00251, Helsinki, Finland.
    Background: Contact urticaria (CU) and protein contact dermatitis (PCD) are mainly induced by an immediate, IgE-mediated immunological mechanism. Immediate sensitization is also linked to asthma and/or allergic rhinitis.

    Objectives: To report causes of work-induced CU and PCD, and to evaluate the occurrence of concomitant airway diseases. Read More

    Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation.
    Sci Immunol 2016 Sep;1(3):eaaf8665
    Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
    Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activity-regulated cytoskeleton-associated protein/activity-regulated gene 3. Read More

    Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis.
    J Invest Dermatol 2017 Dec 31;137(12):2523-2531. Epub 2017 Jul 31.
    Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA. Electronic address:
    The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin. Read More

    ELR+ chemokine-mediated neutrophil recruitment is involved in 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity.
    Clin Exp Pharmacol Physiol 2018 Jan 18;45(1):27-33. Epub 2017 Sep 18.
    Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo, Japan.
    Contact dermatitis is a form of delayed-type hypersensitivity characterized by localized thickening, papules, redness and vesicles of the skin. A model of contact dermatitis involving repeated challenge of a hapten is adapted to assess dermatitis as characterized by skin thickening. Recently, it was reported that neutrophils have crucial roles in contact hypersensitivity. Read More

    Arginase1 Deficiency in Monocytes/Macrophages Upregulates Inducible Nitric Oxide Synthase To Promote Cutaneous Contact Hypersensitivity.
    J Immunol 2017 Sep 26;199(5):1827-1834. Epub 2017 Jul 26.
    Department of Dermatology, Duke University, Durham, NC 27710;
    The innate immune components that modulate allergic contact hypersensitivity (CHS) responses are poorly defined. Using human skin from contact dermatitis patients and a mouse model of CHS, we find that hapten allergens disrupt the Arginase1 (Arg1) and inducible NO synthase (iNOS) dynamic in monocytes/macrophages (mono/MΦ), which renders those cells ineffectual in suppressing skin inflammation. Mice lacking Arg1 in MΦ develop increased CHS characterized by elevated ear thickening, mono/MΦ-dominated dermal inflammation, and increased iNOS and IL-6 expression compared with control mice. Read More

    Contact dermatitis considerations in atopic dermatitis.
    Clin Dermatol 2017 Jul - Aug;35(4):367-374. Epub 2017 Apr 22.
    Department of Dermatology, Loma Linda University, Loma Linda, CA. Electronic address:
    Complex immunologic pathways, influenced by both genetic and environment triggers, contribute to the development of atopic dermatitis and allergic contact dermatitis. Suppressing mechanisms between the Th1-driven allergic contact dermatitis and the Th2-driven atopic dermatitis conditions were thought to reduce the simultaneous expression of both; however, recent evidence indicates that pediatric patients with atopic dermatitis are likely to develop clinically relevant positive patch tests and more likely to react to specific allergens, such as lanolin. We review the potential role of skin barrier defects, such as filaggrin mutations and impaired barrier function, including aberrancies in epidermal pH buffering capabilities, which may promote bacterial biofilms and create an environment favoring sensitization. Read More

    A Case of Ischemia-Induced Perianal Ulceration Mimicking Pyoderma Gangrenosum.
    Skinmed 2017 1;15(3):235-237. Epub 2017 Jun 1.
    Department of Dermatology, Antrim Area Hospital, Antrim, Northern Ireland.
    A 68-year-old woman, with a 75-pack-year smoking history and a history of chronic excess alcohol intake, presented with a 5-week history of worsening perianal pain and ulceration. She recently had an inpatient admission with back pain and urinary tract infection during which she developed diarrhea and fecal incontinence. Initially, the perianal ulceration was diagnosed as severe irritant contact dermatitis and treated with barrier creams and topical clobetasone 17-butyrate 0. Read More

    Identification of unique proteomic signatures in allergic and non-allergic skin disease.
    Clin Exp Allergy 2017 Nov 11;47(11):1456-1467. Epub 2017 Aug 11.
    MedImmune, LLC, Gaithersburg, MD, USA.
    Background: Atopic dermatitis (AD), psoriasis (PS), and contact dermatitis (CD) are common skin diseases, characterized by barrier disruption and systemic inflammation, with unique epidermal signatures and common inflammatory pathways identified by transcriptomic profiling. This study profiled proteomic signatures in serum from subjects with AD, PS, and CD compared with healthy controls (HC).

    Objective: Identify unique proteomic signatures to distinguish between inflammatory diseases with similar epidermal disruption and overlapping epithelial inflammation. Read More

    [Basis for the treatment of eczematous diseases in otorhinolaryngology].
    HNO 2017 Oct;65(10):826-833
    Zentrum für Rhinologie und Allergologie Wiesbaden, An den Quellen 10, 65183, Wiesbaden, Deutschland.
    According to Coombs and Gell, cell-mediated immune responses belong to type IV reactions and are borne mainly by T lymphocytes. The eliciting allergens are usually so-called haptens. Haptens are substances which develop to whole antigens only by binding to protein carriers. Read More

    Of self-lipids, CD1-restricted T cells, and contact sensitization.
    Eur J Immunol 2017 07;47(7):1119-1122
    Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.
    Contact hypersensitivity (CHS) in rodents and contact dermatitis in humans are long-known pathological conditions caused by MHC-restricted T-cell responses. These responses are triggered upon T-cell recognition of neo-antigenic determinants, which are generated by a variety of environmental contact sensitizer (CS) chemicals associating with self-proteins to comprise these neo-antigens. In this issue of the European Journal of Immunology, Betts et al. Read More

    Site-specific regulation of oral mucosa-recruiting CD8+ T cells in a mouse contact allergy model.
    Biochem Biophys Res Commun 2017 09 4;490(4):1294-1300. Epub 2017 Jul 4.
    Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan. Electronic address:
    Contact allergy is a T cell-mediated, delayed-type hypersensitivity generated by contact exposure of an allergen to the skin and mucosal surface. The clinical manifestations of allergic responses between the skin and oral mucosa vary and the differences in immunopathology have not been clarified. We generated hapten-induced contact hypersensitivity (CH) of the buccal mucosa (BM) in parallel studies with ear skin (ES) CH, and observed several characteristic findings of BM CH. Read More

    Allergy and Sexual Behaviours: an Update.
    Clin Rev Allergy Immunol 2017 Jun 26. Epub 2017 Jun 26.
    Department of Internal Medicine, Section of Immunoallergology and Respiratory Diseases, University of Florence, Florence, Italy.
    The exact prevalence of hypersensitivity reactions related to sexual behaviours is not known; however, they heavily impact on the quality of life and of sex life of affected patients. In fact, not only common respiratory and skin allergies, such as asthma, rhinitis, urticaria and atopic dermatitis, but also food and drug allergy have been found to negatively affect the quality of sex life. Allergic diseases impact on the sexual function in both physical and psychological ways, representing one of the main complaints of a considerable proportion of patients. Read More

    Nickel Sulfate Promotes IL-17A Producing CD4+ T Cells by an IL-23-Dependent Mechanism Regulated by TLR4 and Jak-STAT Pathways.
    J Invest Dermatol 2017 Oct 17;137(10):2140-2148. Epub 2017 Jun 17.
    Inflammation Chimiokines et Immunopathologie, INSERM, Fac. de pharmacie-Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France. Electronic address:
    Allergic contact dermatitis, caused by nickel, is a delayed-type hypersensitivity reaction, and 14.5% of the general population may be affected in Europe. Among a wide range of cytokines, the IL-12 family has unique structural and immunological characteristics. Read More

    Occludin Expression in Epidermal γδ T Cells in Response to Epidermal Stress Causes Them To Migrate into Draining Lymph Nodes.
    J Immunol 2017 Jul 31;199(1):62-71. Epub 2017 May 31.
    Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan; and
    Epidermal γδ T cells that reside in the front line of the skin play a pivotal role in stress immune surveillance. However, it is not clear whether these cells are involved in further induction of immune responses after they are activated in dysregulated epidermis. In this study, we found that activated γδ T cells expressed occludin and migrated into draining lymph nodes in an occludin-dependent manner. Read More

    TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells, which decreases in contact hypersensitivity.
    Mol Immunol 2017 Jul 12;87:188-199. Epub 2017 May 12.
    Laboratory of Anti-inflammatory Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address:
    Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5+CD1dhi Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5+CD1dhi Bregs. In this study, we isolated splenocytes or splenic CD19+ B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5+CD1dhi Bregs by flow cytometry. Read More

    Indigo Naturalis Ameliorates Oxazolone-Induced Dermatitis but Aggravates Colitis by Changing the Composition of Gut Microflora.
    Int Arch Allergy Immunol 2017 9;173(1):23-33. Epub 2017 May 9.
    Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
    Background: Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood.

    Methods: A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. Read More

    Rational Tuning of Visual Cycle Modulator Pharmacodynamics.
    J Pharmacol Exp Ther 2017 Jul 5;362(1):131-145. Epub 2017 May 5.
    Department of Pharmacology, School of Medicine (P.D.K., J.Z., K.P.), Department of Chemistry (M.B., G.P.T.), Case Western Reserve University, Cleveland, Ohio; Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio (P.D.K., N.S.P.); Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio (J.K., N.S.P.); and Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio (N.S.P.)
    Modulators of the visual cycle have been developed for treatment of various retinal disorders. These agents were designed to inhibit retinoid isomerase [retinal pigment epithelium-specific 65 kDa protein (RPE65)], the rate-limiting enzyme of the visual cycle, based on the idea that attenuation of visual pigment regeneration could reduce formation of toxic retinal conjugates. Of these agents, certain ones that contain primary amine groups can also reversibly form retinaldehyde Schiff base adducts, which contributes to their retinal protective activity. Read More

    Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide, astrotactin 1-derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis-like and psoriasis-like dermatitis.
    J Allergy Clin Immunol 2018 Jan 26;141(1):137-151. Epub 2017 Apr 26.
    Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea; Research Institute for Natural Sciences, Hanyang University, Seoul, Korea; Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon, Korea. Electronic address:
    Background: Atopic dermatitis (AD) and psoriasis are the 2 most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier.

    Objective: We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating AD and psoriasis. Read More

    E-Cadherin-Mediated Cell Contact Controls the Epidermal Damage Response in Radiation Dermatitis.
    J Invest Dermatol 2017 Aug 26;137(8):1731-1739. Epub 2017 Apr 26.
    Institute of Life Sciences, Fuzhou University, Fuzhou, Fujian, China. Electronic address:
    Radiotherapy is a primary oncological treatment modality that also damages normal tissue, including the skin, and causes radiation dermatitis (RD). Here, we explore the mechanism of acute epidermal damage in radiation dermatitis. Two distinctive phases in the damage response were identified: an early destructive phase, where a burst of reactive oxygen species induces loss of E-cadherin-mediated cell contact, followed by a regenerative phase, during which Wnt and Hippo signaling are activated. Read More

    Contact sensitizers trigger human CD1-autoreactive T-cell responses.
    Eur J Immunol 2017 07 23;47(7):1171-1180. Epub 2017 May 23.
    Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
    Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Read More

    Anti-Inflammatory Effect of Titrated Extract of Centella asiatica in Phthalic Anhydride-Induced Allergic Dermatitis Animal Model.
    Int J Mol Sci 2017 Mar 30;18(4). Epub 2017 Mar 30.
    College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungduk-gu, Cheongju 361-951, Korea.
    Centella asiatica has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. Read More

    Skin sensitizers in cosmetics and beyond: potential multiple mechanisms of action and importance of T-cell assays for in vitro screening.
    Crit Rev Toxicol 2017 May 22;47(5):415-432. Epub 2017 Mar 22.
    a Cosmetics Division, Office of Cosmetics and Colors (OCAC) , Center for Food Safety and Applied Nutrition (CFSAN), Food and Drug Administration (FDA) , MD , USA.
    Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity (DTH) reaction induced by repeated contact with sensitizers. The ability of a chemical to act as a sensitizer has most frequently been tested in animals. As the use of animals for these purposes is gradually and globally being phased out, there is a need for reliable in vitro surrogate assays. Read More

    Roles of alternatively activated M2 macrophages in allergic contact dermatitis.
    Allergol Int 2017 Jul 18;66(3):392-397. Epub 2017 Mar 18.
    Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
    Alternatively activated macrophages (M2 macrophages) play key roles in the suppression of Th1 cell responses and the orchestration of tissue repair. However, recent studies have shown that M2 macrophages have potentials to produce high levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α, suggesting that M2 macrophages may exacerbate inflammation in some settings. In this regard, we have recently shown that large numbers of M2 macrophages accumulate in the sites of hapten-induced contact hypersensitivity (CHS), an animal model of allergic contact dermatitis, and that M2 macrophages exacerbate hapten-induced CHS by producing matrix metalloproteinase 12 (MMP12). Read More

    Immunology and genetics of tumour necrosis factor in allergic contact dermatitis.
    Contact Dermatitis 2017 May 16;76(5):257-271. Epub 2017 Mar 16.
    Department of Dermatology, University Medical Centre Groningen, University of Groningen, 9700 RB, Groningen, The Netherlands.
    During the sensitization phase of allergic contact dermatitis, the proinflammatory cytokine tumour necrosis factor (TNF) plays an important role by promoting epidermal Langerhans cell migration to draining lymph nodes. It also plays a role during the elicitation phase. The TNF gene (TNF) is located within the major histocompatibility complex region. Read More

    Aquaporins in the Skin.
    Adv Exp Med Biol 2017 ;969:173-191
    Department of Physiology, Medical College of Georgia at Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
    The skin is the largest organ of the body, serving as an important barrier between the internal milieu and the external environment. The skin is also one of the first lines of defense against microbial infection and other hazards, and thus, the skin has important immune functions . This organ is composed of many cell types, including immune-active dendritic cells (epidermal Langerhans cells and dermal dendritic cells), connective tissue-generating dermal fibroblasts and pigment-producing melanocytes. Read More

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