Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

J Exp Med. 2021 May 3;218(5):e20200817. doi: 10.1084/jem.20200817.


The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)-induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemo-sensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell-ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU-treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by "sensing" the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Cells, Cultured
  • Fluorouracil / pharmacology*
  • Gene Expression Profiling / methods
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Immunosuppressive Agents / pharmacology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Reverse Transcriptase Polymerase Chain Reaction


  • Immunosuppressive Agents
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Fluorouracil