IL-36R ligands are potent regulators of dendritic and T cells

Vigne, Solenne; Palmer-Lourenco, Gaby; Lamacchia, Céline; Martin, Praxedis Sina; Talabot Frischknecht-Ayer, Dominique; Rodriguez, Emiliana; Ronchi, Francesca; Sallusto, Federica; Dinh, Huyen; Sims, John Ernest; Gabay, Cem

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Title		IL-36R ligands are potent regulators of dendritic and T cells
Authors		Vigne, Solenne Palmer-Lourenco, Gaby Lamacchia, Céline Martin, Praxedis Sina Talabot Frischknecht-Ayer, Dominique Rodriguez, Emiliana Ronchi, Francesca Sallusto, Federica Dinh, Huyen Sims, John Ernest Gabay, Cem show all authors [1 - 11]
Published in		Blood. 2011, vol. 118, no. 22, p. 5813-23
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.
Keywords		Animals — Bone Marrow Cells/drug effects/metabolism/physiology — Cells, Cultured — Dendritic Cells/drug effects/metabolism/physiology — Dose-Response Relationship, Drug — Drug Evaluation, Preclinical — Interleukin-1/pharmacology/physiology — Interleukins/pharmacology/physiology — Ligands — Male — Mice — Mice, Inbred C57BL — Mice, Knockout — Receptors, Interleukin/agonists/antagonists & inhibitors/genetics/metabolism — Receptors, Interleukin-1/agonists/genetics/metabolism — T-Lymphocytes/drug effects/metabolism/physiology
Identifiers		DOI: 10.1182/blood-2011-05-356873 PMID: 21860022
Full text		Article (Published version) (658 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Research group		Mécanisme de l'inflammation articulaire (44)
Citation (ISO format)		VIGNE, Solenne et al. IL-36R ligands are potent regulators of dendritic and T cells. In: Blood, 2011, vol. 118, n° 22, p. 5813-23. https://archive-ouverte.unige.ch/unige:25242