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Distinct expression of interleukin (IL)-36 α, β and γ , their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease

Abstract : Interleukin (IL)-36a, IL-36b and IL-36g 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-36a, g and IL-36Ra, but not IL-36b and IL-38 mRNA, was induced and correlated with IL-1b and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collageninduced arthritis and in the synovium of patients with RA, IL-36a, b, g, IL-36Ra and IL-38 were all elevated and correlated with IL-1b, 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-36a, g and IL-38 were induced at relatively low levels and correlated with IL-1b 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 1 macrophages, dendritic/Langerhans cells and CD79a 1 plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36b and IL-36Ra were produced constitutively, but IL-36a, g 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.
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https://hal-cnrs.archives-ouvertes.fr/hal-03153612
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Submitted on : Wednesday, March 3, 2021 - 10:53:45 AM
Last modification on : Wednesday, April 27, 2022 - 3:58:20 AM

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M.-A. Boutet, G. Bart, M. Penhoat, J. Amiaud, B. Brulin, et al.. Distinct expression of interleukin (IL)-36 α, β and γ , their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease. Clinical and Experimental Immunology, Wiley, 2016, 184 (2), pp.159-173. ⟨10.1111/cei.12761⟩. ⟨hal-03153612⟩

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