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KMT2D maintains Treg homeostasis and protects against inflammatory diseases by regulating the purinergic channel P2X7 [CUT&Tag]

GSE316339 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 5 samples Submitted 2026/01/18 Platform GPL34290
Summary
Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance through the prevention of inflammatory and autoimmune responses. The histone methyltransferase KMT2D is indispensable for induced Treg (iTreg) cell differentiation, its role in the differentiation and function of Treg cells in vivo has remained largely unknown. Here, we demonstrate that KMT2D is critical for the differentiation and function of effector activated Treg (aTreg) cells. We found that KMT2D deficiency in Treg cells impairs aTreg generation and exacerbates inflammatory conditions, such as allergic airway inflammation and colitis. Mechanistically, KMT2D regulates aTreg differentiation through TCR signaling. Furthermore, KMT2D modulates Ca2+ influx by promoting the expression of purinergic receptor P2X7 through H3K4me3 deposition. Collectively, our fundings highlight a pivotal role for KMT2D in Treg cell homeostasis and function, potentially offering a new therapeutic strategy for treating inflammatory diseases.
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Also filed as BioProject PRJNA1402339 and SRA study SRP661875. Searching any of these in the dataset finder brings you back here.

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