Publications by authors named "Munenari Itoh"

42 Publications

Case of disseminated superficial actinic porokeratosis successfully treated with Q-switched ruby laser.

J Dermatol 2021 May 21;48(5):e244-e245. Epub 2021 Mar 21.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.15861DOI Listing
May 2021

Regression of CD30-positive large cell transformation arising on patch lesion of early mycosis fungoides.

Clin Case Rep 2020 Dec 22;8(12):2418-2422. Epub 2020 Jul 22.

Department of Dermatology The Jikei University School of Medicine Tokyo Japan.

CD30-positive large cell transformation that occurs in early mycosis fungoides potentially possesses characteristics of spontaneous regression as with CD30-positive lymphoproliferative disorders. Such transformation may not relate to poor prognosis.
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http://dx.doi.org/10.1002/ccr3.3171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752389PMC
December 2020

Footprint-free gene mutation correction in induced pluripotent stem cell (iPSC) derived from recessive dystrophic epidermolysis bullosa (RDEB) using the CRISPR/Cas9 and piggyBac transposon system.

J Dermatol Sci 2020 Jun 24;98(3):163-172. Epub 2020 Apr 24.

Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a monogenic skin blistering disorder caused by mutations in the type VII collagen gene. A combination of biological technologies, including induced pluripotent stem cells (iPSCs) and several gene-editing tools, allows us to develop gene and cell therapies for such inherited diseases. However, the methodologies for gene and cell therapies must be continuously innovated for safe clinical use.

Objective: In this study, we used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology to correct the pathogenic mutation in RDEB-specific iPSCs, and the piggyBac transposon system so that no residual gene fragments remained in the genome of iPSCs after correcting the mutation.

Methods: For homologous recombination (HR)-based gene editing using CRISPR/Cas9, we designed guide RNA and template DNA including homologous sequences with drug-mediated selection cassette flanked by inverted repeat sequences of the transposon. HR reaction using CRISPR/Cas9 was induced in RDEB-specific iPSCs, and mutation-corrected iPSCs (MC-iPSCs) was obtained. Consequently, the selection cassette in the genome of MC-iPSCs was removed by transposase expression.

Results: After CRISPR/Cas9-induced gene editing, we confirmed that the pathogenic mutation in RDEB-specific iPSCs was properly corrected. In addition, MC-iPSCs had no genetic footprint after removing the selection cassette by transposon system, and maintained their "stemness". When differentiating MC-iPSCs into keratinocytes, the expression of type VII collagen was restored.

Conclusions: Our study demonstrated one of the safer approaches to establish gene and cell therapies for skin hereditary disorders for future clinical use.
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http://dx.doi.org/10.1016/j.jdermsci.2020.04.004DOI Listing
June 2020

Muir-Torre syndrome: sebaceous carcinoma concurrent with colon cancer in a kidney transplant recipient; a case report.

BMC Nephrol 2019 10 29;20(1):394. Epub 2019 Oct 29.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.

Background: Sebaceous carcinoma is a rare but progressive malignant skin cancer, and the incidence is approximately five times higher in post-transplant patients than in people who have not received kidney transplants. Sebaceous carcinoma is sometimes found concurrently with visceral cancers and a genetic abnormality, Muir-Torre syndrome. We report the case of a female kidney transplant recipient with sebaceous carcinoma concurrent with colon cancer 10 years after transplantation.

Case Presentation: A 43-year-old woman was admitted due to a rapidly progressive tumor on her head. Histologically, the tumor was diagnosed as sebaceous carcinoma. We diagnosed her with Muir-Torre syndrome based on the following evidence: 1) high prevalence of microsatellite instability in gene locus assay, 2) absence of mismatch repair proteins in the sebaceous carcinoma on immunohistochemical analysis, and 3) a genetic mutation of 1226_1227delAG in the MSH2 exon 7 in the lesion detected by DNA sequencing analysis. Several reports have shown an association between immunosuppressive agents and latent Muir-Torre syndrome progression. Therefore, the progression of colon cancer in this case originated from her genetic mutation for Muir-Torre syndrome and long-term use of immunosuppressive agents.

Conclusion: This case report not only highlights the importance of adequate diagnosis and therapy for Muir-Torre syndrome, but also suggests the further prevention of the development of malignant tumors in kidney transplant recipients. Physicians should be mindful that sebaceous carcinoma in kidney transplant recipients is highly concurrent with Muir-Torre syndrome.
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http://dx.doi.org/10.1186/s12882-019-1592-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819420PMC
October 2019

Role of interleukin-24 in the tumor-suppressive effects of interferon-β on melanoma.

Exp Dermatol 2019 07 6;28(7):836-844. Epub 2019 Jun 6.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

Background: Type 1 interferons (IFNs), including IFN-β, are widely used in adjuvant therapy for patients who undergo surgery for malignant melanoma to inhibit recurrence and in-transit metastasis. The precise mechanisms underlying the tumor-suppressive effects of IFN-β on melanoma are not yet completely understood.

Objective: The purpose was to reveal the mechanisms underlying the tumor-suppressive effects of IFN-β via interleukin (IL)-24.

Methods: Genome-wide oligonucleotide microarray, quantitative real-time reverse transcription-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and western blotting assay were performed using four melanoma cell lines (A375, RPMI-7951, SK-MEL-5 and SK-MEL-1) treated with natural-type IFN-β to assess the expression of IL-24. Proliferation assay was performed using these melanoma cells and IL-24 knock-down melanoma cells.

Results: Genome-wide microarray analysis detected candidate genes upregulated in IFN-β-sensitive cells after treatment with IFN-β. We focused on IL-24 among the candidate genes encoding secretory proteins. Peak IL-24 mRNA expression completely correlated with the order of sensitivity of melanoma cells to IFN-β. IFN-β treatment induced extracellular IL-24 protein in IFN-β-sensitive cells, but did not induce intracellular IL-24 protein. Knock-down of IL-24 changed melanoma cells into IFN-β-resistant cells. The expression ratio of IL-22R1, one of the IL-24 receptors, correlated with the order of sensitivity of melanoma cells to IFN-β. Treatment with recombinant human IL-24 did not have any effects on all the melanoma cell lines.

Conclusion: Our data suggest that IFN-β suppresses the proliferation of melanoma cells through extracellular IL-24 protein derived from melanoma cells.
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http://dx.doi.org/10.1111/exd.13955DOI Listing
July 2019

Case of ultraviolet B-mediated photosensitivity during the administration of voriconazole.

J Dermatol 2019 09 25;46(9):e327-e328. Epub 2019 Apr 25.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.14874DOI Listing
September 2019

Rituximab-induced vasculitis: Does the immune complex of rituximab play a key role in developing paradoxical adverse events?

J Dermatol 2019 09 10;46(9):e311-e312. Epub 2019 Apr 10.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.14872DOI Listing
September 2019

Hearing loss caused by discoid lupus erythematosus of the ear canal successfully treated with hydroxychloroquine.

J Dermatol 2019 09 1;46(9):e313-e314. Epub 2019 Apr 1.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.14875DOI Listing
September 2019

Novel mutation c.263A>G in the ACVRL1 gene in a Japanese patient with hereditary hemorrhagic telangiectasia 2.

J Dermatol 2019 Jan 20;46(1):e22-e24. Epub 2018 Jun 20.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.14521DOI Listing
January 2019

Introduction of the TERT and BMI1 genes into murine dermal papilla cells ameliorates hair inductive activity.

J Dermatol Sci 2018 May 21;90(2):218-221. Epub 2018 Feb 21.

Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2018.02.003DOI Listing
May 2018

Approach for the Derivation of Melanocytes from Induced Pluripotent Stem Cells.

J Invest Dermatol 2018 01 5;138(1):150-158. Epub 2017 Sep 5.

Institute of Dermatology & Cutaneous Sciences, Sapporo, Japan.

Induced pluripotent stem (iPS) cells have the ability to differentiate into multiple cell types in the body and have an unlimited growth potential. However, iPS cell-derived melanocytes produced by existing protocols have significant limitations in developing novel strategies for regenerative medicine and cell therapies of pigmentation disorders in humans because they involve culture in media containing fetal bovine serum and nonphysiological agents. In this study, we established an in vitro approach to generate iPS cell-derived human melanocytes that have higher proliferation rates and increased melanin production compared with melanocytes prepared by previously reported approaches. Importantly, our iPS cell-derived human melanocytes are prepared in fetal bovine serum-free culture conditions that do not contain any nonphysiological agents. We designed two original methods, transferring black colonies by pipette and recovering black cell pellets from centrifuged medium, and numerous human iPS cell-derived melanocytes proliferated in gelatinous dishes coated with Matrigel after 12 days. We also succeeded in inducing melanin pigmentation in the nude mouse skin in vivo using those human iPS cell-derived melanocytes. We propose that this method using iPS cells established from T cells in the blood of normal human volunteers could be applied clinically to develop regenerative medicine and cell therapies for various forms of human pigmentation disorders.
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http://dx.doi.org/10.1016/j.jid.2017.07.849DOI Listing
January 2018

Successful treatment of ustekinumab in a psoriasis patient with human T-cell leukemia/lymphotropic virus type 1 infection.

J Dermatol 2017 Nov 18;44(11):1334-1335. Epub 2016 Nov 18.

Department of Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.13678DOI Listing
November 2017

A case of deep dissecting hematoma: different managements resulting in similar outcomes.

Int J Dermatol 2016 Dec 6;55(12):e628-e629. Epub 2016 Aug 6.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/ijd.13390DOI Listing
December 2016

Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a patient with recessive dystrophic epidermolysis bullosa (RDEB) carrying two compound heterozygous mutations in the COL7A1 gene.

Stem Cell Res 2016 07 17;17(1):32-35. Epub 2016 May 17.

Department of Dermatology, The Jikei University School of Medicine, Japan.

Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, RDEB-iPSC26, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. RDEB-iPSC26 may be a useful cell resource for the establishment of in vitro RDEB modeling and the study for developing gene and cell therapy.
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http://dx.doi.org/10.1016/j.scr.2016.05.003DOI Listing
July 2016

Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC1.

Stem Cell Res 2016 07 11;17(1):22-24. Epub 2016 May 11.

Department of Dermatology, The Jikei University School of Medicine, Japan.

Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC1, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layers. WT-iPSC1 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs.
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http://dx.doi.org/10.1016/j.scr.2016.05.001DOI Listing
July 2016

Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC4.

Stem Cell Res 2016 07 11;17(1):19-21. Epub 2016 May 11.

Department of Dermatology, The Jikei University School of Medicine.

Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC4, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC4 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs.
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http://dx.doi.org/10.1016/j.scr.2016.05.004DOI Listing
July 2016

Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC2.

Stem Cell Res 2016 07 11;17(1):16-18. Epub 2016 May 11.

Department of Dermatology, The Jikei University School of Medicine, Japan.

Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC2, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC2 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs.
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http://dx.doi.org/10.1016/j.scr.2016.05.002DOI Listing
July 2016

Case of desmoplastic melanoma with lung metastasis maintaining complete response after cessation of nivolumab.

J Dermatol 2017 Mar 27;44(3):e17-e18. Epub 2016 Jul 27.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.13536DOI Listing
March 2017

Cutaneous apocrine carcinoma on the scalp after cranial irradiation for acute lymphocytic leukaemia.

Eur J Dermatol 2016 Dec;26(6):612-613

Department of Dermatology, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo, 105-8461, Japan.

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http://dx.doi.org/10.1684/ejd.2016.2855DOI Listing
December 2016

Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a patient with lymphedema-distichiasis syndrome (LDS) carrying an insertion-deletion complex mutation in the FOXC2 gene.

Stem Cell Res 2016 05 18;16(3):611-3. Epub 2016 Mar 18.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

Expanded human T cells from a Japanese male with lymphedema-distichiasis syndrome (LDS) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, LDS-iPSC8, was confirmed by the expression of stem cell markers and the differentiation capability into three germ layers. LDS-iPSC8 may be a useful cell resource for the establishment of in vitro LDS modeling and the study for vascular and lymph vessel development.
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http://dx.doi.org/10.1016/j.scr.2016.03.004DOI Listing
May 2016

Acquired hemophilia A and fulminant diabetes mellitus possibly caused by adalimumab in a patient with psoriatic arthritis.

J Dermatol 2017 Mar 21;44(3):e3-e4. Epub 2016 May 21.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.13468DOI Listing
March 2017

Thymoma-associated cutaneous graft-versus-host-like disease possibly treated with Narrow-band UVB phototherapy.

Eur J Dermatol 2016 Apr;26(2):208-9

Department of Dermatology The Jikei University School of Medicine 3-25-8 Nishishimbashi, Minato-ku, Tokyo, JAPAN 106-8461.

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http://dx.doi.org/10.1684/ejd.2015.2716DOI Listing
April 2016

A Case of Advanced Extramammary Paget's Disease Successfully Controlled by Monthly but Not Weekly Docetaxel Chemotherapy.

Case Rep Oncol 2016 Jan-Apr;9(1):6-10. Epub 2016 Jan 8.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

Extramammary Paget's disease (EMPD) is an uncommon cutaneous adenocarcinoma arising from the apocrine glands within the epidermis or underlying skin appendages in the anogenital and axillary regions. Surgical excision is basically performed as a treatment for EMPD. However, therapeutic options for EMPD in an advanced stage are limited. Herein, we report the case of a Japanese woman with advanced EMPD successfully controlled by monthly but not weekly docetaxel therapy. We also demonstrate the possibility that a monthly regimen of docetaxel is a more effective and optimal schedule than a weekly one through this case report.
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http://dx.doi.org/10.1159/000443234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748788PMC
March 2016

Case of metachronous and multifocal extramammary Paget's disease.

J Dermatol 2016 Jun 12;43(6):723-4. Epub 2016 Feb 12.

Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.13254DOI Listing
June 2016

Japanese sporadic case of erythrokeratodermia variabilis caused by the connexin-30.3 (GJB4) mutation: Is Glycine 12 a mutational hotspot in the connexin family?

J Dermatol 2016 Jul 30;43(7):830-1. Epub 2016 Jan 30.

Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/1346-8138.13277DOI Listing
July 2016

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

PLoS One 2015 26;10(8):e0136713. Epub 2015 Aug 26.

Department of Dermatology, Columbia University, New York, NY, United States of America; Department of Genetics and Development, Columbia University, New York, NY, United States of America.

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136713PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550351PMC
May 2016

Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro.

J Dermatol Sci 2015 Aug 27;79(2):110-8. Epub 2015 Apr 27.

Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Japan. Electronic address:

Background: The dermal papilla is composed of a small clump of mesenchymal cells, called dermal papilla cells (DPCs). DPCs closely interact with epidermal cells to give rise to hair follicles and shafts during hair follicle development and the hair cycle. DPCs are promising cell sources for hair regeneration therapy for alopecia patients. However, once DPCs are put into conventional two-dimensional culture conditions, they quickly lose their capability to produce hair follicles.

Objective: We aimed to expand a sufficiently large population of DPCs that retain their hair inductive activity.

Methods: Murine DPCs were cultured in the presence of platelet-derived growth factor-AA (PDGF-AA) and fibroblast growth factor 2 (FGF2). Expressions of follicular-related genes were analyzed by real time PCR and hair inductive activity was determined by patch assay and chamber assay in vivo.

Results: FGF2 significantly increased the expression of platelet-derived growth factor receptor alpha (PDGFRα) in cultured vibrissal DPCs. PDGF-AA, a ligand of PDGFRα, promoted proliferation of DPCs synergistically when utilized with FGF2 and enhanced the expression of several follicular-related genes in DPCs. Hair reconstitution assays revealed that DPCs treated with both PDGF-AA and FGF-2 were able to maintain their hair inductive activity better than those treated with FGF2 alone.

Conclusion: Both cell proliferation and hair inductive activity in murine DPCs are maintained by the synergistic effect of FGF2 and PDGF-AA.
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http://dx.doi.org/10.1016/j.jdermsci.2015.04.007DOI Listing
August 2015

Reduction of interleukin-10 production by B cells in intractable toxic epidermal necrolysis.

J Dermatol 2015 Aug 11;42(8):804-8. Epub 2015 May 11.

Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Several interleukin (IL)-10 producing B-cell subsets have been identified recently. However, few studies have examined the role of them in toxic epidermal necrolysis (TEN). We describe a 41-year-old woman with TEN who had B-cell lymphoma and a history of treatments including B-cell depletion therapy. Her re-epithelization was still ongoing after 7 months, despite treatments. To investigate her immune system, we compared cytokine and chemokine production from B cells and non-B cells isolated from the patient and another non-lymphoma TEN patient. IL-10 production from B cells decreased in the patient compared with the control TEN-only patient. Cytokine and chemokine levels from non-B cells involved in inflammation were elevated in the patient compared with the control patient. In conclusion, this study demonstrates that IL-10 from B cells as well as regulatory T cells is critical in the pathogenesis of TEN, and that B-cell dysfunction based on B-cell lymphoma and B-cell depletion therapy may be involved in the intractability of TEN.
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http://dx.doi.org/10.1111/1346-8138.12909DOI Listing
August 2015
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