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CCR2 deficiency alters activation of microglia subsets in traumatic brain injury

2021; Cell Press; Volume: 36; Issue: 12 Linguagem: Inglês

10.1016/j.celrep.2021.109727

2639-1856

Kerri Somebang, Joshua Rudolph, Isabella Imhof, Luyi Li, Eréne C. Niemi, Judy K. Shigenaga, Huy Tran, Thomas M. Gill, Iris Lo, Brian A. Zabel, Gabriela Schmajuk, Brian T. Wipke, Stefka Gyoneva, Luke Jandreski, Michael Craft, Gina Benedetto, Edward D. Plowey, Israel Charo, James J. Campbell, Chun Ye, S. Scott Panter, Mary C. Nakamura, Walter L. Eckalbar, Christine L. Hsieh,

Immune Response and Inflammation

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.