Liver type 1 innate lymphoid cells develop locally via an interferon-γ–dependent loop

An IFN-γ feedback loop Innate lymphoid cells (ILCs) play important roles in tissue homeostasis and host defense. Type 1 ILCs (ILC1s) produce interferon-γ (IFN-γ) and require the transcriptional master regulator T-bet. The pathways underlying how these cells develop and differentiate have remained poorly understood. Bai et al. found that the adult mouse liver contains a population of Lin–Sca-1 + Mac-1 + hematopoietic stem cells (LSM HSCs) that preferentially differentiate into tissue-resident liver ILC1s. They further show that IFN-γ produced by mature ILC1s promotes the expansion and differentiation of LSM HSCs into ILC1s but not natural killer cells. This work expands our understanding of extramedullary hematopoiesis and underscores the unique immune status of the liver. Science , this issue p. eaba4177