Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A is not known. Here, we found that adherent IBD-associated microbiota induced TL1A release from CX3CR1+ mononuclear phagocytes (MNPs). Using cell-specific genetic deletion models, we identified an essential role for CX3CR1+MNP-derived TL1A in driving group 3 innate lymphoid cell (ILC3) production of interleukin-22 and mucosal healing during acute colitis. In contrast to this protective role in acute colitis, TL1A-dependent expression of co-stimulatory molecule OX40L in MHCII+ ILC3s during colitis led to co-stimulation of antigen-specific T cells that was required for chronic T cell colitis. These results identify a role for ILC3s in activating intestinal T cells and reveal a central role for TL1A in promoting ILC3 barrier immunity during colitis.

中文翻译：

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微生物群诱导的TNF样配体1A驱动第3组结肠炎期间先天淋巴细胞介导的屏障保护和肠T细胞活化。

炎症性肠病（IBD）是由微生物群和遗传易感宿主之间相互作用失调导致的。遗传研究已将TNFSF15多态性及其蛋白类TNF配体1A（TL1A）与IBD联系起来，但TL1A的功能作用尚不清楚。在这里，我们发现粘附的IBD相关微生物群诱导TL1A从CX3CR1 +单核吞噬细胞（MNPs）释放。使用特定于细胞的遗传删除模型，我们确定了CX3CR1 + MNP衍生的TL1A在驱动3组白细胞介素22和急性结肠炎期间黏膜愈合的先天淋巴样细胞（ILC3）产生中的重要作用。与急性结肠炎的这种保护作用相反，结肠炎期间MHCII + ILC3中TL1A依赖性共刺激分子OX40L的表达导致共刺激慢性T细胞结肠炎所需的抗原特异性T细胞。这些结果确定了ILC3在激活肠T细胞中的作用，并揭示了TL1A在结肠炎过程中促进ILC3屏障免疫的重要作用。