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

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.

• Authors: M-A Boutet, G Bart, M Penhoat, J Amiaud, B Brulin, C Charrier, F Morel, J-C Lecron, M Rolli-Derkinderen, A Bourreille, S Vigne, C Gabay, G Palmer, B Le Goff, F Blanchard
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 184 Issue 2 Pg. 159-73 (May 2016) ISSN: 1365-2249 [Electronic] England
• PMID: 26701127 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 British Society for Immunology.

Chemical References

• Aminoquinolines
• IL-38 protein, human
• IL36A protein, human
• IL36B protein, human
• IL36G protein, human
• IL36RN protein, human
• Interleukin-1
• Interleukins
• RNA, Messenger
• Imiquimod

Topics

• Aminoquinolines
• Animals
• Arthritis, Experimental (immunology, pathology)
• Arthritis, Rheumatoid (immunology, pathology)
• Caco-2 Cells
• Cell Line
• Crohn Disease (immunology, pathology)
• Dendritic Cells (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Humans
• Imiquimod
• Inflammation (immunology, pathology)
• Interleukin-1 (biosynthesis, genetics)
• Interleukins (biosynthesis, genetics)
• Intestinal Mucosa (cytology, metabolism)
• Keratinocytes (metabolism)
• Macrophages (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Plasma Cells (metabolism)
• Psoriasis (immunology, pathology)
• RNA, Messenger (biosynthesis)
• Skin (metabolism)
• Synovial Membrane (cytology, metabolism)
• Th17 Cells (immunology)