N-acetyltransferase 10 is implicated in the pathogenesis of cycling T cell-mediated autoimmune and inflammatory disorders in mice.

T cell expansion has a crucial function in both autoimmune and chronic inflammatory diseases, with cycling T cells contributing to the pathogenesis of autoimmune diseases by causing uncontrolled immune responses and tissue damage. Yet the regulatory mechanisms governing T cell expansion remain incompletely understood. Here we show that the enzyme N-acetyltransferase 10 (NAT10) regulates T cell activation and proliferation upon antigen stimulation. T cell-specific NAT10 deficiency in mice reduces the number of mature T cells in peripheral lymphoid organs. Mechanistically, NAT10 acetylates RACK1 at K185, preventing subsequent RACK1 K48-linked ubiquitination and degradation. The increased RACK1 stability alters ribosome formation and cellular metabolism, leading to enhanced supply of energy and biosynthetic precursors and, eventually, T cell proliferation. Our findings thus highlight the essential function of NAT10 in T cell self-renewal and metabolism and elucidate NAT10 mode of action for the potential development of novel therapies for immune-related disorders. Abnormal T cell proliferation often triggers autoimmune disorders. Here the authors show that T cell-specific deficiency of the enzyme N-acetyltransferase 10 ameliorates experimental autoimmune encephalitis potentially by RACK1-mediated regulation of T cell metabolism and expansion. [ABSTRACT FROM AUTHOR]