Protective ILC1s

Immunity https://doi.org/10.1016/j.immuni.2019.11.004 (2019)

ILC1s are the dominant subset of innate lymphoid cells (ILCs) in the liver. In Immunity, Nabekura et al. show that acute liver injury triggered by injection with carbon tetrachloride (CCl₄) activates ILC1s to produce the cytokine interferon-γ (IFN-γ), which in turn promotes the survival of hepatocytes. NK1.1⁺DX5^–CD49a⁺CD200R⁺ ILC1s, but not NK1.1⁺DX5⁺CD49a^–CD200R^– natural killer (NK) cells, NKT cells, αβ T cells, γδ T cells or MAIT (mucosa-associated invariant T) cells, make IFN-γ, and depletion of liver ILC1s or deletion of Ifng increases the amount of alanine aminotransferase in the serum—a measure of liver injury—after injection of CCl₄ or acetaminophen. Production of IFN-γ in ILC1s is dependent on the expression of the NK receptor DNAM-1 (CD226) on these cells, is induced by the cytokine IL-12 and extracellular ATP and, in turn, upregulates the expression of the prosurvival molecules Bcl2 and Bcl-x_L in hepatocytes. Transferred ILC1s protect Rag2^–/–Il2r^–/– mice from CCl₄-induced liver injury, indicating that ILC1s are necessary and sufficient in this context.