The endoplasmic reticulum associated degradation adaptor Sel1L regulates T cell homeostasis and function

Summary Suppressor/Enhancer of Lin-12-like (Sel1L) is a critical adaptor for endoplasmic reticulum-associated degradation (ERAD), a process that maintains cellular protein quality control through degradation of misfolded proteins. Here we investigate the role of Sel1L in T cell homeostasis and function. T cell-specific deletion of Sel1L profoundly impairs peripheral T cell survival and promotes apoptotic cell death. Furthermore, Sel1L is required to maintain na?ve CD8+ T cell homeostasis in a cell-intrinsic manner with loss of quiescence as evidenced by increased proliferation. Sel1L-deficient T cells exhibit enhanced activation of the mammalian target of rapamycin (mTOR) pathway and altered cellular metabolism, including increased cellular reactive oxygen species, mitochondrial mass and mitochondrial membrane potential in the na?ve CD8+ T cell compartment. Furthermore, loss of Sel1L impaired CD8+ T cell immune responses following bacterial infection. These results demonstrate a novel role for Sel1L/ERAD in T cell homeostasis and function.