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

Nat Commun. 2024 Oct 30;15(1):9388. doi: 10.1038/s41467-024-53350-x.

Abstract

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.

MeSH terms

  • Animals
  • Autoimmune Diseases* / immunology
  • Cell Proliferation
  • Humans
  • Inflammation / immunology
  • Lymphocyte Activation* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • N-Terminal Acetyltransferase E / genetics
  • N-Terminal Acetyltransferase E / immunology
  • N-Terminal Acetyltransferase E / metabolism
  • T-Lymphocytes* / immunology
  • Ubiquitination

Substances

  • N-Terminal Acetyltransferase E