ACC1 determines memory potential of individual CD4+ T cells by regulating de novo fatty acid biosynthesis

Nat Metab. 2019 Feb;1(2):261-275. doi: 10.1038/s42255-018-0025-4. Epub 2019 Jan 14.

Abstract

Immunological memory is central to adaptive immunity and protection from disease. Changing metabolic demands as antigen-specific T cells transition from effector to memory cells have been well documented, but the cell-specific pathways and molecules that govern this transition are poorly defined. Here we show that genetic deletion of ACC1, a rate-limiting enzyme in fatty acid biosynthesis, enhances the formation of CD4+ T memory cells. ACC1-deficient effector helper T (Th) cells have similar metabolic signatures to wild-type memory Th cells, and expression of the gene encoding ACC1, Acaca, was inversely correlated with a memory gene signature in individual cells. Inhibition of ACC1 function enhances memory T cell formation during parasite infection in mice. Using single-cell analyses we identify a memory precursor-enriched population (CCR7hiCD137lo) present during early differentiation of effector CD4+ T cells. Our data indicate that fatty acid metabolism directs cell fate determination during the generation of memory CD4+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / physiology*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Lineage
  • Fatty Acids / biosynthesis*
  • Immunologic Memory / physiology*
  • Mice
  • Mice, Inbred BALB C

Substances

  • Fatty Acids
  • ACC1 protein, mouse
  • Acetyl-CoA Carboxylase