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Clin Exp Immunol. 2016 May;184(2):159-73. doi: 10.1111/cei.12761. Epub 2016 Feb 22.

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

Author information

1
INSERM, UMR 957, Nantes, France.
2
Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.
3
Rheumatology Unit, Nantes University Hospital, Nantes, France.
4
EA 4331, University of Poitiers, Poitiers, France.
5
Service Immunologie/Inflammation, Poitiers University Hospital, Poitiers, France.
6
INSERM, UMR 913, Nantes, France.
7
Service d'Hépato-Gastroentérologie, Nantes University Hospital, Nantes, France.
8
Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva and Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.

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.

KEYWORDS:

Crohn's disease; IL-36; psoriasis; rheumatoid arthritis

PMID:
26701127
PMCID:
PMC4837235
DOI:
10.1111/cei.12761
[Indexed for MEDLINE]
Free PMC Article

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