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

Nature Metabolism
Yusuke EndoToshinori Nakayama

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.

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Citations

Jul 6, 2020·International Immunology·Alok Kumar, Kenji Chamoto
May 28, 2019·Immunology and Cell Biology·David O'Sullivan
Aug 15, 2020·Frontiers in Immunology·Akane S SuzukiToshinori Nakayama
May 1, 2019·Clinical and Experimental Immunology·L J PallettA Schurich

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Methods Mentioned

BETA
flow cytometry
PMA
enzyme-linked immunosorbent assay
ELISA
PCA
fluorescence-activated cell sorting
FACS
RNA-seq
chip
electrophoresis

Software Mentioned

SINGuLar
SINGuLar Analysis Toolsets
Graphpad Prism
GeneChip Operating Software ( GCOS )
BioMark system
Bowtie
Metabolome
Fluidigm
BioMark Realtime PCR analysis
TopHat

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