IL-36R ligands are potent regulators of dendritic and T cells
IL-36R ligands are potent regulators of dendritic and T cells
复制标题
DOI：
10.1182/blood-2011-05-356873
复制
发表时间：
2011-11-24
期刊：
影响因子：
20.3
通讯作者：
Gabay, Cem
中科院分区：
文献类型：
--
作者：
Vigne, Solenne;Palmer, Gaby;Gabay, Cem
IL-36 α (IL-1F6)、IL-36 β (IL-1F8) 和 IL-36 γ (IL-1F9) 是 IL-1 细胞因子家族的成员。这些细胞因子与 IL-36R (IL-1Rrp2) 和 IL-1RAcP 结合，激活与 IL-1 类似的细胞内信号，而 IL-36Ra (IL-1F5) 则充当 IL-36R 拮抗剂 (IL-36Ra)。在这项研究中，我们发现小鼠骨髓源性树突状细胞（BMDC）和CD4（+）T淋巴细胞组成型表达IL-36R并对IL-36α、IL-36β和IL-36γ做出反应。 IL-36 诱导 BMDC 产生促炎细胞因子，包括 IL-12、IL-1 beta、IL-6、TNF-α 和 IL-23，其刺激作用比其他 IL-1 细胞因子更有效。此外，IL-36β增强了BMDC的CD80、CD86和MHC II类的表达。 IL-36还诱导CD4(+)T细胞和培养的脾细胞产生IFN-γ、IL-4和IL-17。当以 100 至 1000 倍摩尔过量使用时，这些刺激作用会被 IL-36Ra 拮抗。用 IL-36 β 免疫小鼠显着且特异性地促进 Th1 反应。因此，我们的数据表明 IL-36R 配体在先天免疫和适应性免疫之间的界面中发挥着关键作用，从而刺激 T 辅助细胞反应。 （血。2011；118(22):5813-5823）
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)