Tmem127-mediated immune receptor recycling regulates T cell homeostasis through the common gamma chain
Maintenance of T cell population size is important for immune homeostasis. It is achieved by providing limited survival cues: interleukin-7 (IL-7) and low-affinity TCR-MHC interactions. Using arrayed CRISPR screening, we have identified adaptor protein Tmem127 as an essential regulator of multiple T cell surface markers. Combining Bio-ID and proteomics, we detected Tmem127 in proximity to and regulating the abundance of 15 proteins, among which we validated interaction with a common gamma chain (IL-2R?, ?c, CD132). Through regulation of surface IL-7 receptor levels, Tmem127 controls the naïve and central memory T cell population sizes by restricting homeostatic proliferation in vitro and in vivo. While Tmem127 germline knockout (KO) mice are healthy, they have increased spleen size and faster induction of experimental autoimmune encephalomyelitis (EAE).