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Distinct expression of interleukin (IL)-36[alpha], [beta] and [gamma], their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease

Summary Interleukin (IL)-36[alpha], IL-36[beta] and IL-36[gamma] are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in r...

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Published in:Clinical and experimental immunology 2016-05, Vol.184 (2), p.159
Main Authors: Boutet, M-A, Bart, G, Penhoat, M, Amiaud, J, Brulin, B, Charrier, C, Morel, F, Lecron, J-C, Rolli-Derkinderen, M, Bourreille, A, Vigne, S, Gabay, C, Palmer, G, Le Goff, B, Blanchard, F
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Language:English
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Summary:Summary Interleukin (IL)-36[alpha], IL-36[beta] and IL-36[gamma] are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36[alpha], [gamma] and IL-36Ra, but not IL-36[beta] and IL-38 mRNA, was induced and correlated with IL-1[beta] and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36[alpha], [beta], [gamma], IL-36Ra and IL-38 were all elevated and correlated with IL-1[beta], CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36[alpha], [gamma] and IL-38 were induced at relatively low levels and correlated with IL-1[beta] and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68+ macrophages, dendritic/Langerhans cells and CD79[alpha]+ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36[beta] and IL-36Ra were produced constitutively, but IL-36[alpha], [gamma] and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.
ISSN:0009-9104
1365-2249
DOI:10.1111/cei.12761