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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.

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.

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.
Source :
Clinical & Experimental Immunology. May2016, Vol. 184 Issue 2, p159-173. 15p.
Publication Year :
2016

Abstract

Interleukin (IL)-36α, IL-36β and IL-36γ 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-36α, γ and IL-36Ra, but not IL-36β and IL-38 mRNA, was induced and correlated with IL-1β 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-36α, β, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1β, 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-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1β 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 CD79α+ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36β and IL-36Ra were produced constitutively, but IL-36α, γ 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00099104
Volume :
184
Issue :
2
Database :
Academic Search Index
Journal :
Clinical & Experimental Immunology
Publication Type :
Academic Journal
Accession number :
114639957
Full Text :
https://doi.org/10.1111/cei.12761