Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

被引：38

作者：

Sudo, Takao ^{[1
,2
,3
]}

Motomura, Yasutaka ^{[2
,4
,5
]}

Okuzaki, Daisuke ^{[6
,7
]}

Hasegawa, Tetsuo ^{[1
]}

Yokota, Takafumi ^{[3
]}

Kikuta, Junichi ^{[1
,2
,8
]}

Ao, Tomoka ^{[1
,8
]}

Mizuno, Hiroki ^{[1
,2
]}

Matsui, Takahiro ^{[1
,9
]}

Motooka, Daisuke ^{[6
,7
]}

Yoshizawa, Ryosuke ^{[1
]}

Nagasawa, Takashi ^{[2
,10
]}

Kanakura, Yuzuru ^{[3
]}

Moro, Kazuyo ^{[2
,4
,5
]}

Ishii, Masaru ^{[1
,2
,8
]}

机构：

[1] Osaka Univ, Grad Sch Med & Frontier Biosci, Dept Immunol & Cell Biol, Osaka, Japan

[2] Osaka Univ, World Premier Int Res Ctr Initiat Immunol Frontie, Osaka, Japan

[3] Osaka Univ, Dept Hematol & Oncol, Grad Sch Med, Osaka, Japan

[4] Osaka Univ, Grad Sch Med, Dept Microbiol & Immunol, Lab Innate Immune Syst, Osaka, Japan

[5] RIKEN Ctr Integrat Med Sci, Lab Innate Immune Syst, Yokohama, Kanagawa, Japan

[6] Osaka Univ, World Premier Int Res Ctr Initiat Immunol Frontie, Single Cell Genom, Human Immunol, Osaka, Japan

[7] Osaka Univ, Microbial Dis Res Inst, Genome Informat Res Ctr, Osaka, Japan

[8] Natl Inst Biomed Innovat Hlth & Nutr, Lab Bioimaging & Drug Discovery, Osaka, Japan

[9] Osaka Univ, Dept Pathol, Grad Sch Med, Osaka, Japan

[10] Osaka Univ, Grad Sch Med & Frontier Biosci, Lab Stem Cell Biol & Dev Immunol, Osaka, Japan

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2021年 / 218卷 / 05期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

COLONY-STIMULATING FACTOR; BONE-MARROW NICHE; STEM-CELLS; GM-CSF; MYELOID PROGENITOR; INFLAMMATION; REGENERATION; ENGRAFTMENT; QUIESCENCE; DIFFERENTIATION;

D O I：

10.1084/jem.20200817

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：21

共 73 条

[1] Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].