Group 2 Innate Lymphoid Cells Support Hematopoietic Recovery Under Stress Conditions

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2021 Mar 5

PMID 33666647

Citations 25

Authors

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

Affiliations

Soon will be listed here.

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.

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