Setd2 supports GATA3(+)ST2(+) thymic-derived Treg cells and suppresses intestinal inflammation.
Setd2 supports GATA3(+)ST2(+) thymic-derived Treg cells and suppresses intestinal inflammation.
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DOI：
10.1038/s41467-022-35250-0
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发表时间：
2022-12-03
影响因子：
16.6
通讯作者：
Qiu, Ju
中科院分区：
文献类型：
--
作者：
Ding, Zhaoyun;Cai, Ting;Tang, Jupei;Sun, Hanxiao;Qi, Xinyi;Zhang, Yunpeng;Ji, Yan;Yuan, Liyun;Chang, Huidan;Ma, Yanhui;Zhou, Hong;Li, Li;Sheng, Huiming;Qiu, Ju
Treg细胞获得独特的转录特性以抑制特异性炎症反应。Treg细胞的转录特征受表观遗传修饰的调节，其机制尚不清楚。在这里，我们报告Setd 2，一种组蛋白H3 K36甲基转移酶，对Treg细胞的存活和抑制功能很重要，特别是那些来自肠道的Treg细胞。Setd 2通过促进GATA 3和ST 2在tTreg细胞中的表达和相互关系来支持GATA 3 + ST 2+肠胸腺源性Treg（tTreg）细胞。IL-33优先增强Foxp 3Cre-YFPSetd 2 flox/flox小鼠中的Th 2细胞而不是GATA 3 + Treg细胞，证实了Treg细胞中Setd 2表达对Th 2应答的限制。SETD 2维持人Treg细胞中的GATA 3表达，并且SETD 2表达在来自人结肠直肠癌组织的Treg细胞中增加。表观遗传学上，Setd 2通过调节启动子和基因内增强子的活性来调节靶基因（包括Il 1 rl 1）的转录，其中H3 K36 me 3通常沉积在基因内增强子中。我们的研究结果为Setd 2调节Treg细胞和肠道免疫提供了机制性见解。Treg细胞可以通过表观遗传调节剂在功能上改变。在这里，作者表明组蛋白H3 K36甲基转移酶Setd 2对于Treg细胞的存活和调节小鼠中IL-33介导的Th 2应答是重要的，并且在来自人结直肠癌组织的Treg细胞中，Setd 2表达增加。
Treg cells acquire distinct transcriptional properties to suppress specific inflammatory responses. Transcription characteristics of Treg cells are regulated by epigenetic modifications, the mechanism of which remains obscure. Here, we report that Setd2, a histone H3K36 methyltransferase, is important for the survival and suppressive function of Treg cells, especially those from the intestine. Setd2 supports GATA3+ST2+ intestinal thymic-derived Treg (tTreg) cells by facilitating the expression and reciprocal relationship of GATA3 and ST2 in tTreg cells. IL-33 preferentially boosts Th2 cells rather than GATA3+ Treg cells in Foxp3Cre-YFPSetd2 flox/flox mice, corroborating the constraint of Th2 responses by Setd2 expression in Treg cells. SETD2 sustains GATA3 expression in human Treg cells, and SETD2 expression is increased in Treg cells from human colorectal cancer tissues. Epigenetically, Setd2 regulates the transcription of target genes (including Il1rl1) by modulating the activity of promoters and intragenic enhancers where H3K36me3 is typically deposited. Our findings provide mechanistic insights into the regulation of Treg cells and intestinal immunity by Setd2. Treg cells can be functionally altered by epigenetic modulators. Here the authors show that the histone H3K36 methyltransferase Setd2 is important for the survival of Treg cells and for the regulation of IL-33 mediated Th2 responses in mice and SETD2 expression is increased in Treg cells from human colorectal cancer tissue.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
30.5
作者：
Kitagawa Y;Ohkura N;Kidani Y;Vandenbon A;Hirota K;Kawakami R;Yasuda K;Motooka D;Nakamura S;Kondo M;Taniuchi I;Kohwi-Shigematsu T;Sakaguchi S
通讯作者：
Sakaguchi S
影响因子：
16.8
作者：
de Almeida, Sergio Fernandes;Grosso, Ana Rita;Carmo-Fonseca, Maria
通讯作者：
Carmo-Fonseca, Maria
DOI：
10.1073/pnas.1815016116
发表时间：
2019-02-12
影响因子：
11.1
作者：
Ameri, Amir H.;Tuchayi, Sara Moradi;Demehri, Shadmehr
通讯作者：
Demehri, Shadmehr
影响因子：
4.3
作者：
Copsel, Sabrina;Wolf, Dietlinde;Levy, Robert B.
通讯作者：
Levy, Robert B.