Setd2 supports GATA3ST2 thymic-derived Treg cells and suppresses intestinal inflammation.

Dec 5, 2022

Contributor: Zhaoyun Ding,Ting Cai,Jupei Tang,Hanxiao Sun,Xinyi Qi,Yunpeng Zhang,Yan Ji,Liyun Yuan,Huidan Chang,Yanhui Ma,Hong Zhou,Li Li,Huiming Sheng,Ju Qiu

Setd2 supports GATA3ST2 thymic-derived Treg cells and suppresses intestinal inflammation.

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 GATA3ST2 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 Foxp3Setd2 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.
© 2022. The Author(s).

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About The Expert

Zhaoyun Ding

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Ting Cai

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510180, China.

Jupei Tang

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Hanxiao Sun

Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.

Xinyi Qi

Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200025, China.

Yunpeng Zhang

Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.

Yan Ji

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Liyun Yuan

CAS Key Laboratory of Computational Biology, Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Science, Shanghai, 200031, China.

Huidan Chang

CAS Key Laboratory of Computational Biology, Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Science, Shanghai, 200031, China.

Yanhui Ma

Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Hong Zhou

School of Life Science, Anhui Medical University, Hefei, 241000, China.

Li Li

State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China. lil@sjtu.edu.cn.

Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China. lil@sjtu.edu.cn.

Huiming Sheng

Department of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China. HMSHENG@shsmu.edu.cn.

Ju Qiu

CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. qiuju@sibs.ac.cn.

References

PubMed