Monocyte-derived IL-6 programs microglia to rebuild damaged brain vasculature.
Nat Immunol
; 24(7): 1110-1123, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37248420
ABSTRACT
Cerebrovascular injury (CVI) is a common pathology caused by infections, injury, stroke, neurodegeneration and autoimmune disease. Rapid resolution of a CVI requires a coordinated innate immune response. In the present study, we sought mechanistic insights into how central nervous system-infiltrating monocytes program resident microglia to mediate angiogenesis and cerebrovascular repair after an intracerebral hemorrhage. In the penumbrae of human stroke brain lesions, we identified a subpopulation of microglia that express vascular endothelial growth factor A. These cells, termed 'repair-associated microglia' (RAMs), were also observed in a rodent model of CVI and coexpressed interleukin (IL)-6Ra. Cerebrovascular repair did not occur in IL-6 knockouts or in mice lacking microglial IL-6Ra expression and single-cell transcriptomic analyses revealed faulty RAM programming in the absence of IL-6 signaling. Infiltrating CCR2+ monocytes were the primary source of IL-6 after a CVI and were required to endow microglia with proliferative and proangiogenic properties. Faulty RAM programming in the absence of IL-6 or inflammatory monocytes resulted in poor cerebrovascular repair, neuronal destruction and sustained neurological deficits that were all restored via exogenous IL-6 administration. These data provide a molecular and cellular basis for how monocytes instruct microglia to repair damaged brain vasculature and promote functional recovery after injury.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Stroke
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2023
Type:
Article
Affiliation country:
United States