ILC3-derived OX40L is essential for homeostasis of intestinal Tregs in immunodeficient mice
ILC3-derived OX40L is essential for homeostasis of intestinal Tregs in immunodeficient mice
复制标题
ILC3 衍生的 OX40L 对于免疫缺陷小鼠肠道 Tregs 的稳态至关重要。
DOI：
10.1038/s41423-019-0200-x
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发表时间：
2020-02-01
影响因子：
24.1
通讯作者：
Qiu, Ju
中科院分区：
文献类型：
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作者：
Deng, Tian;Suo, Caixia;Qiu, Ju
0X 40 L是可由脾淋巴组织诱导（Lti）细胞表达的共刺激分子之一，脾淋巴组织诱导（Lti）细胞是第3组先天淋巴样细胞（ILC 3）的子集。肠ILC 3亚群中OX 40 L的表达和ILC 3中OX 40 L表达的分子调控尚不清楚。在这里，我们显示了在所有肠白细胞中标记为OX 40 L（高）群体的肠ILC 3，并且是Rag 1（-/-）小鼠中OX 40 L的主要来源。所有ILC 3亚群均表达OX 40 L，NCR（-）ILC 3是OX 40 L的最丰富来源。ILC 3s中OX 40 L的表达在炎症过程中上调。除了肿瘤坏死因子（TNF）样细胞因子1A（TL 1A），这已被称为OX 40 L的触发器，我们发现，Poly（I：C）代表病毒刺激促进OX 40 L的表达在ILC 3通过细胞自主的方式。此外，我们证明了IL-7-STAT 5信号传导通过ILC 3维持OX 40 L表达。肠调节性T细胞（TCRs），其中大部分表达OX 40，有缺陷的扩增嵌合小鼠，其中ILC 3是专门缺乏OX 40 L的表达。同时，在小肠的隐睾组织中发现了TcR和ILC 3的共定位，这表明ILC 3和TcR之间存在密切的相互作用。我们的研究揭示了粘膜组织中TCLs和ILC 3之间通过OX 40-OX 40 L信号传导的串扰，这对肠道TCLs的稳态至关重要。
OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer (Lti) cells, a subset of group 3 innate lymphoid cells (ILC3s). OX40L expression in subsets of intestinal ILC3s and the molecular regulation of OX40L expression in ILC3s are unknown. Here, we showed intestinal ILC3s marked as an OX40L(high) population among all the intestinal leukocytes and were the dominant source of OX40L in Rag1(-/-) mice. All ILC3 subsets expressed OX40L, and NCR(-)ILC3s were the most abundant source of OX40L. The expression of OX40L in ILC3s could be upregulated during inflammation. In addition to tumor necrosis factor (TNF)-like cytokine 1A (TL1A), which has been known as a trigger for OX40L, we found that Poly (I:C) representing viral stimulus promoted OX40L expression in ILC3s via a cell-autonomous manner. Furthermore, we demonstrated that IL-7-STAT5 signaling sustained OX40L expression by ILC3s. Intestinal regulatory T cells (Tregs), most of which expressed OX40, had defective expansion in chimeric mice, in which ILC3s were specifically deficient for OX40L expression. Consistently, co-localization of Tregs and ILC3s was found in the cryptopatches of the intestine, which suggests the close interaction between ILC3s and Tregs. Our study has unveiled the crosstalk between Tregs and ILC3s in mucosal tissues through OX40-OX40L signaling, which is crucial for the homeostasis of intestinal Tregs.