RIPK1 plays a crucial role in maintaining regulatory T cell homeostasis by inhibiting both RIPK3 and FADD-mediated cell death
Regulatory T (Treg) cells are a critical for maintaining immune balance in various physiological and pathological conditions. However, the mechanisms underlying Treg homeostasis remain incompletely understood. In this study, we demonstrated that RIPK1 is crucial for Treg cell survival and homeostasis. We generated mice with Treg cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the number of Treg cell caused by excessive cell death. Unlike conventional T cells, Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking the FADD pathway. However, simultaneous removal of both Fadd and Ripk3 completely restored the number of Ripk1-deficient Treg cells by blocking cell death. Our results demonstrated that RIPK1 plays a critical role in regulating Treg cell survival by controlling both necroptosis and apoptosis. These findings provide new insights into the mechanisms of Treg cell homeostasis and suggest potential therapeutic targets for autoimmune diseases. Overall design: Spleen and peripheral lymph nodes were harvested in Foxp3-YFP-Cre and Ripk1fl/fl Foxp3-YFP-Cre mice. For RNAseq, We have four samples, WT rTreg, WT aTreg, cKO rTreg, cKO aTreg.