HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production
HMGB1 exacerbates experimental mouse colitis by enhancing innate lymphoid cells 3 inflammatory responses via promoted IL-23 production
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HMGB1 通过促进 IL-23 的产生来增强先天淋巴细胞 3 炎症反应，从而加剧实验性小鼠结肠炎。
DOI：
10.1177/1753425916669862
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发表时间：
2016-11-01
期刊：
影响因子：
3.2
通讯作者：
Fang, Min
中科院分区：
文献类型：
--
作者：
Chen, Xiangyu;Li, Lingyun;Fang, Min
在炎症性肠病（IBD）中，高迁移率族蛋白1（HMGB 1）作为一种内源性炎症分子，可通过作用于TLR 2/4，促进炎症细胞因子的分泌，导致组织损伤。其潜在机制尚不清楚。在这里，我们报告了一个新的作用，HMGB 1在控制的维持和功能的丝氨酸居民组3先天淋巴细胞（ILC 3），是重要的先天效应细胞参与粘膜稳态和IBD的发病机制。我们发现，用抗HMGB 1抗体治疗的小鼠，或TLR 2（-/-）或TLR 4（-/-）基因缺陷的小鼠，显示出肠道炎症减少。在这些小鼠中，结肠ILC 3的数量显著减少，并且结肠组织中ILC 3可分泌的IL-17和IL-22的水平也降低。此外，HMGB 1通过TLR 2/4信号转导促进DC产生IL-23，激活ILC 3产生IL-17和IL-22。提示HMGB 1-TLR 2/4-DCs-IL-23级联途径可增强ILC 3s产生IL-17和IL-22的功能，该信号途径可能在IBD的发生发展中起重要作用。
In inflammatory bowel diseases (IBD), high mobility group box 1 (HMGB1), as an endogenous inflammatory molecule, can promote inflammatory cytokines secretion by acting on TLR2/4 resulting in tissue damage. The underlying mechanisms remain unclear. Here we report a novel role of HMGB1 in controlling the maintenance and function of intestine-resident group-3 innate lymphoid cells (ILC3s) that are important innate effector cells implicated in mucosal homeostasis and IBD pathogenesis. We showed that mice treated with anti-HMGB1 Ab, or genetically deficient for TLR2(-/-) or TLR4(-/-) mice, displayed reduced intestinal inflammation. In these mice, the numbers of colonic ILC3s were significantly reduced, and the levels of IL-17 and IL-22 that can be secreted by ILC3s were also decreased in the colon tissues. Furthermore, HMGB1 promoted DCs via TLR2/4 signaling to produce IL-23, activating ILC3s to produce IL-17 and IL-22. Our data thus indicated that the HMGB1-TLR2/4-DCs-IL-23 cascade pathway enhances the functions of ILC3s to produce IL-17 and IL-22, and this signal way might play a vital role in the development of IBD.