Setd2 supports GATA3<sup>+</sup>ST2<sup>+</sup> thymic-derived Treg cells and suppresses intestinal inflammation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36463230.
- Also identified by DOI 10.1038/s41467-022-35250-0 and PMC identifier 9719510.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>+</sup>ST2<sup>+</sup> 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<sup>+</sup> Treg cells in Foxp3<sup>Cre-YFP</sup>Setd2 <sup>flox/flox</sup> 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.
Medical subject headings
- Histone-Lysine N-Methyltransferase
- Interleukin-1 Receptor-Like 1 Protein
- T-Lymphocytes, Regulatory
- Intestines