title: In Vivo Expansion of Activated Foxp3+ Regulatory T Cells and Establishment of a Type 2 Immune Response upon IL-33 Treatment Protect against Experimental Arthritis.
abstract: IL-33 is strongly involved in several inflammatory and autoimmune disorders with both pro- and anti-inflammatory properties. However, its contribution to chronic autoimmune inflammation, such as rheumatoid arthritis, is ill defined and probably requires tight regulation. In this study, we aimed at deciphering the complex role of IL-33 in a model of rheumatoid arthritis, namely, collagen-induced arthritis (CIA). We report that repeated injections of IL-33 during induction (early) and during development (late) of CIA strongly suppressed clinical and histological signs of arthritis. In contrast, a late IL-33 injection had no effect. The cellular mechanism involved in protection was related to an enhanced type 2 immune response, including the expansion of eosinophils, Th2 cells, and type 2 innate lymphoid cells, associated with an increase in type 2 cytokine levels in the serum of IL-33-treated mice. Moreover, our work strongly highlights the interplay between IL-33 and regulatory T cells (Tregs), demonstrated by the dramatic in vivo increase in Treg frequencies after IL-33 treatment of CIA. More importantly, Tregs from IL-33-treated mice displayed enhanced capacities to suppress IFN-γ production by effector T cells, suggesting that IL-33 not only favors Treg proliferation but also enhances their immunosuppressive properties. In concordance with these observations, we found that IL-33 induced the emergence of a CD39(high) Treg population in a ST2L-dependent manner. Our findings reveal a powerful anti-inflammatory mechanism by which IL-33 administration inhibits arthritis development.
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: Jérôme
authors.initials: J
authors.lastname: Biton
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: Sara
authors.initials: S
authors.lastname: Khaleghparast Athari
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: Allan
authors.initials: A
authors.lastname: Thiolat
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: François
authors.initials: F
authors.lastname: Santinon
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: Delphine
authors.initials: D
authors.lastname: Lemeiter
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: Roxane
authors.initials: R
authors.lastname: Hervé
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France;
authors.forename: Laure
authors.initials: L
authors.lastname: Delavallée
authors.affiliation: INSERM U1082, Pôle Biologie Santé, Centre Hospitalo-Universitaire Poitiers, BP 633, F-86022 Poitiers, France;
authors.forename: Anais
authors.initials: A
authors.lastname: Levescot
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale CNRS-Université de Toulouse III, F-31000 Toulouse, France; and.
authors.forename: Stéphane
authors.identifier: 0000-0003-3840-3887
authors.initials: S
authors.lastname: Roga
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France;
authors.forename: Patrice
authors.initials: P
authors.lastname: Decker
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale CNRS-Université de Toulouse III, F-31000 Toulouse, France; and.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Girard
authors.affiliation: INSERM U1082, Pôle Biologie Santé, Centre Hospitalo-Universitaire Poitiers, BP 633, F-86022 Poitiers, France;
authors.forename: André
authors.identifier: 0000-0002-9907-2818
authors.initials: A
authors.lastname: Herbelin
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France; Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service de Rhumatologie, F-93009 Bobigny, France.
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
authors.affiliation: INSERM, U1125, F-93017 Bobigny, France; Sorbonne Paris Cité Université Paris 13, F-93000 Bobigny, France; natacha.bessis@univ-paris13.fr.
authors.forename: Natacha
authors.initials: N
authors.lastname: Bessis
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001081:Apyrase / Q000235:genetics; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D003094:Collagen / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004804:Eosinophils; D000067596:Interleukin-33 / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D000067596:Interleukin-33; D003094:Collagen; D001081:Apyrase; C067869:CD39 antigen