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Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

Journal J. Exp. Med. 218(5):e20200817 (2021)
Title Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions
Laboratory Laboratory of Immunology and Cell Biology〈Prof. ISHII Masaru〉
Abstract

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.

Authors

Takao Sudo (1, 2, 3), Yasutaka Motomura (2, 4, 5), Daisuke Okuzaki (6, 7), Tetsuo Hasegawa (1), Takafumi Yokota (3), Junichi Kikuta (1, 2, 8), Tomoka Ao (1, 8), Hiroki Mizuno (1, 2), Takahiro Matsui (1, 9), Daisuke Motooka (6, 7), Ryosuke Yoshizawa (1), Takashi Nagasawa (2, 10), Yuzuru Kanakura (3), Kazuyo Moro (2, 4, 5), Masaru Ishii (1, 2, 8)

  1. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan.
  2. World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  3. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
  4. Laboratory for Innate Immune Systems, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
  5. Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
  6. Single Cell Genomics, Human Immunology, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Osaka, Japan.
  7. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
  8. Laboratory of Bioimaging and Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
  9. Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
  10. Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan.
PubMed 33666647

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