Open AccessGroup 2 innate lymphoid cells support hematopoietic recovery under stress conditions
Author(s) -
Takao Sudo,
Yasutaka Motomura,
Daisuke Okuzaki,
Tetsuo Hasegawa,
Takafumi Yokota,
Junichi Kikuta,
Tomoka Ao,
Hiroki Mizuno,
Takahiro Matsui,
Daisuke Motooka,
Ryosuke Yoshizawa,
Takashi Nagasawa,
Yuzuru Kanakura,
Kazuyo Moro,
Masaru Ishii
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200817
Subject(s) - haematopoiesis , innate lymphoid cell , progenitor cell , bone marrow , biology , adoptive cell transfer , immunology , stem cell , granulocyte , secretion , myeloid , microbiology and biotechnology , hematopoietic stem cell , cancer research , innate immune system , endocrinology , t cell , immune system
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.