期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 19, 期 5, 页码 634-643出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-022-00849-2
关键词
Regulatory T cell; Cell migration; Immune tolerance
类别
资金
- National Key R&D Program of China [2018YFC1003900]
- National Natural Science Foundation of China [82001653, 31970828]
- Jiangsu Outstanding Young Investigator Program [BK20200030]
Regulatory T cells play important roles in maintaining immune homeostasis and immune tolerance during pregnancy. This study revealed the critical role of H3K36me2 methyltransferase Nsd2 in Treg recruitment at the maternal-fetal interface. Loss of Nsd2 disrupted maternal-fetal immune tolerance, leading to severe fetal loss.
Regulatory T cells (Tregs) are fundamentally important for maintaining systemic immune homeostasis and are also required for immune tolerance at the maternal-fetal interface during pregnancy. Recent studies have suggested that epigenetic regulation is critically involved in Treg development and function. However, the role of H3K36me has not yet been investigated. Here, we found that the H3K36me2 methyltransferase Nsd2 was highly expressed in Tregs. Although loss of Nsd2 did not impair systemic Treg development or function, the level of Tregs at the maternal-fetal interface was significantly decreased in pregnant Nsd2 conditional knockout mice. Consequently, maternal-fetal immune tolerance was disrupted in the absence of Nsd2 in Tregs, and the pregnant mice showed severe fetal loss. Mechanistically, Nsd2 was found to upregulate CXCR4 expression via H3K36me2 modification to promote Treg cell recruitment into the decidua and suppress the anti-fetal immune response. Overall, our data identified Nsd2 as a critical epigenetic regulator of Treg recruitment for maternal-fetal tolerance.
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