CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity.

ABSTRACT: Nutrients are emerging regulators of adaptive immunity¹. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism^2-4, but how these environmental signals are integrated for immune regulation remains unclear. Here we use genome-wide CRISPR screening combined with protein-protein interaction networks to identify regulatory modules that mediate immune receptor- and nutrient-dependent signalling to mTORC1 in mouse regulatory T (T_reg) cells. SEC31A is identified to promote mTORC1 activation by interacting with the GATOR2 component SEC13 to protect it from SKP1-dependent proteasomal degradation. Accordingly, loss of SEC31A impairs T cell priming and T_reg sup

SUBMITTER: Long L 

PROVIDER: S-EPMC8887674 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature