Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions.
Animals
Bone Marrow
/ drug effects
Bone Marrow Cells
/ cytology
Cells, Cultured
Fluorouracil
/ pharmacology
Gene Expression Profiling
/ methods
Granulocyte-Macrophage Colony-Stimulating Factor
/ genetics
Hematopoietic Stem Cell Transplantation
/ methods
Hematopoietic Stem Cells
/ cytology
Immunity, Innate
/ drug effects
Immunosuppressive Agents
/ pharmacology
Lymphocytes
/ drug effects
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Confocal
Reverse Transcriptase Polymerase Chain Reaction
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
03 05 2021
03 05 2021
Historique:
received:
27
04
2020
revised:
29
10
2020
accepted:
02
02
2021
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
5
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33666647
pii: 211857
doi: 10.1084/jem.20200817
pmc: PMC7941180
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021 Sudo et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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