title: IL-36R ligands are potent regulators of dendritic and T cells.
abstract: IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) are members of the IL-1 family of cytokines. These cytokines bind to IL-36R (IL-1Rrp2) and IL-1RAcP, activating similar intracellular signals as IL-1, whereas IL-36Ra (IL-1F5) acts as an IL-36R antagonist (IL-36Ra). In this study, we show that both murine bone marrow-derived dendritic cells (BMDCs) and CD4(+) T lymphocytes constitutively express IL-36R and respond to IL-36α, IL-36β, and IL-36γ. IL-36 induced the production of proinflammatory cytokines, including IL-12, IL-1β, IL-6, TNF-α, and IL-23 by BMDCs with a more potent stimulatory effect than that of other IL-1 cytokines. In addition, IL-36β enhanced the expression of CD80, CD86, and MHC class II by BMDCs. IL-36 also induced the production of IFN-γ, IL-4, and IL-17 by CD4(+) T cells and cultured splenocytes. These stimulatory effects were antagonized by IL-36Ra when used in 100- to 1000-fold molar excess. The immunization of mice with IL-36β significantly and specifically promoted Th1 responses. Our data thus indicate a critical role of IL-36R ligands in the interface between innate and adaptive immunity, leading to the stimulation of T helper responses.
authors.affiliation: Division of Rheumatology and Department of Pathology-Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Solenne
authors.initials: S
authors.lastname: Vigne
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.forename: Céline
authors.initials: C
authors.lastname: Lamacchia
authors.forename: Praxedis
authors.initials: P
authors.lastname: Martin
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.forename: Emiliana
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronchi
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.forename: Huyen
authors.initials: H
authors.lastname: Dinh
authors.forename: John E
authors.initials: JE
authors.lastname: Sims
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D007375:Interleukin-1; D007378:Interleukins; D008024:Ligands; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; C502352:IL-1F8 protein, mouse; C569167:IL1F9 protein, mouse; C543716:interleukin 1F6, mouse; C569500:Il1rl2 protein, mouse