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

Science. 2021 Mar 26;371(6536):eaba4177. doi: 10.1126/science.aba4177.


The pathways that lead to the development of tissue-resident lymphocytes, including liver type 1 innate lymphoid cells (ILC1s), remain unclear. We show here that the adult mouse liver contains Lin-Sca-1+Mac-1+ hematopoietic stem cells derived from the fetal liver. This population includes Lin-CD122+CD49a+ progenitors that can generate liver ILC1s but not conventional natural killer cells. Interferon-γ (IFN-γ) production by the liver ILC1s themselves promotes the development of these cells in situ, through effects on their IFN-γR+ liver progenitors. Thus, an IFN-γ-dependent loop drives liver ILC1 development in situ, highlighting the contribution of extramedullary hematopoiesis to regional immune composition within the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hematopoiesis, Extramedullary
  • Immunity, Innate
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Liver / cytology*
  • Liver / immunology*
  • Lymphocytes / cytology*
  • Lymphocytes / immunology*
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / metabolism
  • Lymphopoiesis
  • Mice
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism
  • Signal Transduction
  • T-Box Domain Proteins / metabolism


  • IFNG protein, mouse
  • Receptors, Interferon
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • interferon gamma receptor
  • Interferon-gamma