Journal
CELL REPORTS
Volume 36, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109727
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Funding
- Department of Veterans Affairs Biomedical Laboratory RD [BX002690]
- NIH [R00 HL135403, R01AR071522, R01AI136972, U01HG012192]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR066735, P30AR070155]
- Russell/Engelman Rheumatology Research Center at UCSF
- United States Department of Veterans Affairs Biomedical Laboratory R&D (BLRD) Service [I01 BX004115]
- Chan Zuckerberg Initiative
- Department of Veterans Affairs Biomedical Laboratory RD Merit Award [BX002994]
- S. Scott Panter Research Fund
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In traumatic brain injury, various types of myeloid cells play different roles in either exacerbating damage or assisting in healing. Through single-cell RNA sequencing analysis, multiple subsets of microglia, monocyte/macrophage, and dendritic cells were identified in acute TBI and normal brains, providing new therapeutic targets for brain trauma treatment.
In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2(-/-) mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains. We find alterations in transcriptional profiles of microglia subsets in Ccr2(-/-) TBI mice compared to WT TBI mice indicating that infiltrating monocytes/macrophages influence microglia activation to promote a type I IFN response. Preclinical pharmacological blockade of hCCR2 after injury reduces expression of IFN-responsive gene, Irf7, and improves outcomes. These data extend our understanding of myeloid cell diversity and crosstalk in brain trauma and identify therapeutic targets in myeloid subsets.
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