Research ArticleIMMUNOLOGY

M-CSF, IL-6, and TGF-β promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery

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Science Advances  12 Mar 2021:
Vol. 7, no. 11, eabb6260
DOI: 10.1126/sciadv.abb6260


Traumatic brain injury (TBI) leads to high mortality rate. We aimed to identify the key cytokines favoring TBI repair and found that patients with TBI with a better outcome robustly increased concentrations of macrophage colony-stimulating factor, interleukin-6, and transforming growth factor–β (termed M6T) in cerebrospinal fluid or plasma. Using TBI mice, we identified that M2-like macrophage, microglia, and endothelial cell were major sources to produce M6T. Together with the in vivo tracking of mCherry+ macrophages in zebrafish models, we confirmed that M6T treatment accelerated blood-borne macrophage infiltration and polarization toward a subset of tissue repair macrophages that expressed similar genes as microglia for neuroprotection, angiogenesis and cell migration. M6T therapy in TBI mice and zebrafish improved neurological function while blocking M6T-exacerbated brain injury. Considering low concentrations of M6T in some patients with poor prognostic, M6T treatment might repair TBI via generating a previously unidentified subset of tissue repair macrophages.

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