Inflammation-Induced Lactate Leads to Rapid Loss of Hepatic Tissue-Resident NK Cells

Garvin Dodard, Angela Tata, Timothy K. Erick, Diego Jaime, S. M.Shahjahan Miah, Linda Quatrini, Bertrand Escalière, Sophie Ugolini, Eric Vivier, Laurent Brossay

Research output: Contribution to journalArticlepeer-review

Abstract

The liver harbors two main innate lymphoid cell (ILC) populations: conventional NK (cNK) cells and tissue-resident NK (trNK) cells. Using the MCMV model of infection, we find that, in contrast to liver cNK cells, trNK cells initially undergo a contraction phase followed by a recovery phase to homeostatic levels. The contraction is MCMV independent because a similar phenotype is observed following poly(I:C)/CpG or α-GalCer injection. The rapid contraction phase is due to apoptosis, whereas the recovery phase occurs via proliferation in situ. Interestingly, trNK cell apoptosis is not mediated by fratricide and not induced by liver lymphocytes or inflammatory cytokines. Instead, we find that trNK cell apoptosis is the consequence of an increased sensitivity to lactic acid. Mechanistic analysis indicates that trNK cell sensitivity to lactate is linked to impaired mitochondrial function. These findings underscore the distinctive properties of the liver-resident NK cell compartment.

Original languageEnglish
Article number107855
JournalCell Reports
Volume32
Issue number1
DOIs
Publication statusPublished - Jul 7 2020

Keywords

  • ILC1
  • lactate
  • MCMV
  • mitochondria
  • NK cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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