The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21—A basis for therapeutic JAK1 inhibition

التفاصيل البيبلوغرافية
العنوان: The inflammation in cutaneous lichen planus is dominated by IFN‐ϒ and IL‐21—A basis for therapeutic JAK1 inhibition
المؤلفون: Iris Schäfer, Farzan Solimani, Kamran Ghoreschi, Leticia Quintanilla-Martinez, Eva Müller-Hermelink, Katharina Meier, Katharina Pietschke, Julia Holstein, Franziska C Ghoreschi, Irene Gonzalez-Menendez
بيانات النشر: Freie Universität Berlin, 2020.
سنة النشر: 2020
مصطلحات موضوعية: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, medicine.medical_treatment, animal diseases, Gene Expression, Biochemistry, 030207 dermatology & venereal diseases, 0302 clinical medicine, Interleukin 23, Child, lichen planus, Interleukin-17, psoriasis, Middle Aged, Immunohistochemistry, Interleukin 10, IL-17, Cytokine, STAT1 Transcription Factor, Cytokines, Tumor necrosis factor alpha, Female, Interleukin 17, medicine.symptom, Adult, Adolescent, immune signature, Inflammation, Dermatology, 03 medical and health sciences, Interferon-gamma, Young Adult, medicine, Humans, RNA, Messenger, Molecular Biology, Interleukin 4, Aged, JAK inhibitors, business.industry, Interleukins, Interleukin-8, Janus Kinase 1, bacterial infections and mycoses, stomatognathic diseases, 030104 developmental biology, Immunology, IL17A, business
الوصف: Cutaneous lichen planus (CLP) and psoriasis (PSO) are both common chronic inflammatory skin diseases for which development of new treatments requires the identification of key targets. While PSO is a typical Th17/IL-17-disorder, there is some evidence that Th1/IFN-ɣ dominate the inflammatory process in CLP. Nonetheless, the immunopathogenesis of CLP is not fully explained and key immunological factors still have to be recognized. In this study, we compared the immune signature of CLP lesions with the well-characterized inflammation present in PSO skin. First, we analysed the histological and immunohistological characteristics of CLP and PSO. Second, we assessed the cytokine expression (IL1A, IL1B, IL4, IL6, IL8, IL10, IL17A, IL19, IL21, IL22, IL23A, IL13, IFNG, TNF, IL12A, IL12B and IL36G) of lesional skin of CLP with PSO by qPCR. Histology revealed a similar epidermal thickness in CLP and PSO. Immunohistochemically, both diseases presented with an inflammatory infiltrate mainly composed by CD3+ CD4+ T cells rather than CD3+ CD8+ . Importantly, mRNA analysis showed a distinct cytokine signature: while levels of IL12B, IL1A, IL6 and IL23 were similar between the two groups, the characteristic PSO-associated cytokines IL8, IL17A, IL22, IL19 and IL36G were expressed at very low levels in CLP. In contrast, CLP lesional skin was dominated by the expression of IFNG, IL21, IL4, IL12A and TNF. Immunohistochemistry confirmed the dominance of IL-21, IFN-ɣ and also pSTAT1 in the dermal infiltrate of CLP, while IL-17A was more present in PSO. Collectively, this study improves our understanding of the immunological factors dominating CLP. The dominating cytokines and signalling proteins identified suggest that anti-cytokine therapeutics like JAK inhibitors may be beneficial in CLP.
اللغة: English
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::966feaabbcc398aaa3c1d3021793f7c0Test
https://doi.org/10.1111/exd.14226Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....966feaabbcc398aaa3c1d3021793f7c0
قاعدة البيانات: OpenAIRE