Group 3 innate lymphoid cells (ILC3s), a subset of the innate lymphoid cells, are abundantly present in the intestine and are crucial regulators of intestinal inflammation. Brg1 (Brahma-related gene 1), a catalytic subunit of the mammalian SWI-SNF-like chromatin-remodeling BAF complex, regulates the development and function of various immune cells. Here, by genetic deletion of Brg1 in ILC3s (Smarca4^ΔILC3), we prove that Brg1 supports the differentiation of NKp46⁺ILC3s by promoting the T-bet expression in NKp46⁻ILC3s, which facilitates the conversion of NKp46⁻ILC3s to NKp46⁺ILC3s. Strikingly, Smarca4^ΔILC3 mice of the Rag1^−/− background develop spontaneous colitis accompanied with increased GM-CSF production in ILC3s. By construction of a mixed bone marrow chimeric system, we demonstrate that Brg1 enhances T-bet and inhibits GM-CSF expression in ILC3s through a cell-intrinsic manner. Blockade of GM-CSF ameliorates colitis in Rag1^−/−Smarca4^ΔILC3 mice, suggesting that the suppression of GM-CSF production from ILC3s by Brg1 serves as a critical mechanism for Brg1 to restrain intestinal inflammation. We have further demonstrated that Brg1 binds to the Tbx21 and Csf2 gene locus in ILC3s, and favors the active and repressive histones modifications on gene locus of Tbx21 and Csf2 respectively. Our work reveals the essential role of Brg1 in intestinal immunity by regulating ILC3s.

第 3 组先天性淋巴样细胞 (ILC3s) 是先天性淋巴样细胞的一个子集，大量存在于肠道中，是肠道炎症的重要调节因子。Brg1（Brahma 相关基因 1）是哺乳动物 SWI-SNF 样染色质重塑 BAF 复合物的催化亚基，可调节各种免疫细胞的发育和功能。在这里，通过 ILC3s ( Smarca4 ^ΔILC3 )中 Brg1 的遗传缺失，我们证明 Brg1 通过促进 NKp46 - ILC3s 中的 T-bet 表达支持 NKp46 ⁺ ILC3s 的^分化，这促进了 NKp46 ^- ILC3s 向 NKp46 ⁺ ILC3s 的转化。引人注目的是， Rag1 ^-/-的Smarca4 ^ΔILC3小鼠背景发展自发性结肠炎伴随着 ILC3 中 GM-CSF 产量的增加。通过构建混合骨髓嵌合系统，我们证明 Brg1 通过细胞内在方式增强 T-bet 并抑制 ILC3 中的 GM-CSF 表达。阻断GM-CSF 可改善Rag1 ^-/- Smarca4 ^ΔILC3小鼠的结肠炎，表明 Brg1 抑制 ILC3 产生 GM-CSF 是 Brg1 抑制肠道炎症的关键机制。我们进一步证明 Brg1 与 ILC3 中的Tbx21和Csf2基因位点结合，并有利于对Tbx21和Csf2基因位点的活性和抑制性组蛋白修饰分别。我们的工作通过调节 ILC3 揭示了 Brg1 在肠道免疫中的重要作用。