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

被引：299

作者：

Vigne, Solenne ^{[1
,2
]}

Palmer, Gaby ^{[1
,2
]}

Lamacchia, Celine ^{[1
,2
]}

Martin, Praxedis ^{[1
,2
]}

Talabot-Ayer, Dominique ^{[1
,2
]}

Rodriguez, Emiliana ^{[1
,2
]}

Ronchi, Francesca ^{[3
]}

Sallusto, Federica ^{[3
]}

Dinh, Huyen ^{[4
]}

Sims, John E. ^{[4
]}

Gabay, Cem ^{[1
,2
]}

机构：

[1] Univ Geneva, Sch Med, Div Rheumatol, CH-1211 Geneva, Switzerland

[2] Univ Geneva, Sch Med, Dept Pathol Immunol, CH-1211 Geneva, Switzerland

[3] Biomed Res Inst, Bellinzona, Switzerland

[4] Amgen Inc, Dept Inflammat Res, Seattle, WA USA

来源：

BLOOD | 2011年 / 118卷 / 22期

基金：

瑞士国家科学基金会;

关键词：

INTERLEUKIN-1 RECEPTOR ANTAGONIST; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; IL-1; FAMILY; INFLAMMATORY MEDIATORS; BIOLOGICAL-PROPERTIES; MAST-CELLS; C-FOS; MEMBERS; CYTOKINES;

D O I：

10.1182/blood-2011-05-356873

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

IL-36 alpha (IL-1F6), IL-36 beta (IL-1F8), and IL-36 gamma (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-36 alpha, IL-36 beta, and IL-36 gamma. IL-36 induced the production of proinflammatory cytokines, including IL-12, IL-1 beta, IL-6, TNF-alpha, and IL-23 by BMDCs with a more potent stimulatory effect than that of other IL-1 cytokines. In addition, IL-36 beta enhanced the expression of CD80, CD86, and MHC class II by BMDCs. IL-36 also induced the production of IFN-gamma, 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-36 beta 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. (Blood. 2011;118(22):5813-5823)

引用

页码：5813 / 5823

页数：11

共 38 条

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