연사 소개

약력 

2023. 09 ~ 현재               vascular research center, IBS KAIST, Daejeon, Korea                                        Research fellow

2020. 07 ~ 2023.07      National Institute of Neurological Disorders and Stroke, MD, USA              Postdoctoral fellow

강의 제목

Neuroimmunology in cerebrovascular repair after stroke

강의 내용

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. 

관련 논문

1. Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury

P Mastorakos, N Mihelson, M Luby, SR Burks, K Johnson, AW Hsia, ...Nature neuroscience 24 (2), 245-258