Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

Author:

Sudo Takao123ORCID,Motomura Yasutaka245ORCID,Okuzaki Daisuke67ORCID,Hasegawa Tetsuo1ORCID,Yokota Takafumi3ORCID,Kikuta Junichi128ORCID,Ao Tomoka18ORCID,Mizuno Hiroki12ORCID,Matsui Takahiro19ORCID,Motooka Daisuke67ORCID,Yoshizawa Ryosuke1ORCID,Nagasawa Takashi210ORCID,Kanakura Yuzuru3ORCID,Moro Kazuyo245ORCID,Ishii Masaru128ORCID

Affiliation:

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

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.

Funder

Japan Science and Technology Agency

Japan Society for the Promotion of Science

Takeda Science Foundation

Osaka Cancer Society

Japanese Society of Hematology

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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