title: 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.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.
authors.forename: M-A
authors.initials: MA
authors.lastname: Boutet
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.|Rheumatology Unit, Nantes University Hospital, Nantes, France.
authors.forename: G
authors.initials: G
authors.lastname: Bart
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.|Rheumatology Unit, Nantes University Hospital, Nantes, France.
authors.forename: M
authors.initials: M
authors.lastname: Penhoat
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.
authors.forename: J
authors.initials: J
authors.lastname: Amiaud
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.
authors.forename: B
authors.initials: B
authors.lastname: Brulin
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.
authors.forename: C
authors.initials: C
authors.lastname: Charrier
authors.affiliation: EA 4331, University of Poitiers, Poitiers, France.
authors.forename: F
authors.initials: F
authors.lastname: Morel
authors.affiliation: EA 4331, University of Poitiers, Poitiers, France.|Service Immunologie/Inflammation, Poitiers University Hospital, Poitiers, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Lecron
authors.affiliation: INSERM, UMR 913, Nantes, France.
authors.forename: M
authors.initials: M
authors.lastname: Rolli-Derkinderen
authors.affiliation: INSERM, UMR 913, Nantes, France.|Service d'Hépato-Gastroentérologie, Nantes University Hospital, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Bourreille
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Vigne
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Gabay
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Palmer
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.|Rheumatology Unit, Nantes University Hospital, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Le Goff
authors.affiliation: INSERM, UMR 957, Nantes, France.|Laboratoire De Physiopathologie De La Résorption Osseuse, Faculté De Médecine, Université De Nantes, Nantes Atlantique Universités.
authors.forename: F
authors.initials: F
authors.lastname: Blanchard
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D018938:Caco-2 Cells; D002460:Cell Line; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010950:Plasma Cells / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000634:Aminoquinolines; C571243:IL-38 protein, human; C508586:IL36A protein, human; C508588:IL36B protein, human; C508589:IL36G protein, human; C122187:IL36RN protein, human; D007375:Interleukin-1; D007378:Interleukins; D012333:RNA, Messenger; D000077271:Imiquimod
keywords: Crohn's disease; IL-36; psoriasis; rheumatoid arthritis