Journal
IMMUNITY
Volume 54, Issue 6, Pages 1123-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2021.05.007
Keywords
-
Categories
Funding
- National Key Research and Development Program of China [2019YFA0508503, 2020YFA0509101]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB29030102]
- National Natural Science Foundation of China [U20A20359, 81821001, 31770991, 91742202]
- Fundamental Research Funds for the Central Universities
- University Synergy Innovation Program of Anhui Province [GXXT-2019-026]
Ask authors/readers for more resources
Neutrophils play critical roles in tissue repair by stimulating the activation of ILC3s through the release of lysophosphatidylserine from apoptotic neutrophils, leading to enhanced IL-22 production and tissue repair. Deficiency of the GPR34 receptor in ILC3s limits IL-22 production and tissue repair in response to dying neutrophils, highlighting the importance of the interaction between neutrophils and ILC3s in tissue repair processes.
Neutrophils migrate rapidly to damaged tissue and play critical roles in host defense and tissue homeostasis. Here we investigated the mechanisms whereby neutrophils participate in tissue repair. In an intestinal epithelia injury model, neutrophil depletion exacerbated colitis and associated with reduced interleukin (IL)-22 and limited activation of type 3 innate lymphoid cells (ILC3s). Co-culture with neutrophils activated ILC3s in a manner dependent on neutrophil apoptosis. Metabolomic analyses revealed that lysophosphatidylserine (LysoPS) from apoptotic neutrophils directly stimulated ILC3 activation. ILC3-specific deletion of Gpr34, encoding the LysoPS receptor GPR34, or inhibition of downstream PI3K-AKT or ERK suppressed IL-22 production in response to apoptotic neutrophils. Gpr34(-/-) mice exhibited compromised ILC3 activation and tissue repair during colon injury, and neutrophil depletion abrogated these defects. GPR34 deficiency in ILC3s limited IL-22 production and tissue repair in vivo in settings of colon and skin injury. Thus, GPR34 is an ILC3-expressed damage-sensing receptor that triggers tissue repair upon recognition of dying neutrophils.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available