Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-γ Secretion for Upregulating Bcl-xL Expression in Hepatocytes

Immunity. 2020 Jan 14;52(1):96-108.e9. doi: 10.1016/j.immuni.2019.11.004. Epub 2019 Dec 3.


Although type 1 innate lymphoid cells (ILC1s) have been originally found as liver-resident ILCs, their pathophysiological role in the liver remains poorly investigated. Here, we demonstrated that carbon tetrachloride (CCl4) injection into mice activated ILC1s, but not natural killer (NK) cells, in the liver. Activated ILC1s produced interferon-γ (IFN-γ) and protected mice from CCl4-induced acute liver injury. IFN-γ released from activated ILC1s promoted the survival of hepatocytes through upregulation of Bcl-xL. An activating NK receptor, DNAM-1, was required for the optimal activation and IFN-γ production of liver ILC1s. Extracellular adenosine triphosphate accelerated interleukin-12-driven IFN-γ production by liver ILC1s. These findings suggest that ILC1s are critical for tissue protection during acute liver injury.

Keywords: ATP; Bcl-xL; CCl(4); DNAM-1; IFN-γ; IL-12; IL-7; ILC1; acute liver injury; hepatocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Carbon Tetrachloride / toxicity
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Female
  • Hepatocytes / metabolism*
  • Interferon-gamma / immunology*
  • Interleukin-12 Subunit p35 / immunology
  • Killer Cells, Natural / immunology
  • Liver / cytology*
  • Liver / immunology
  • Liver / injuries
  • Lymphocyte Activation / immunology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • bcl-X Protein / metabolism*


  • Antigens, Differentiation, T-Lymphocyte
  • Bcl2l1 protein, mouse
  • CD226 antigen
  • IFNG protein, mouse
  • Il12a protein, mouse
  • Interleukin-12 Subunit p35
  • bcl-X Protein
  • Interferon-gamma
  • Adenosine Triphosphate
  • Carbon Tetrachloride