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Benakis, C.* ; Simats, A.* ; Tritschler, S. ; Heindl, S.* ; Besson-Girard, S.* ; Llovera, G.* ; Pinkham, K.* ; Kolz, A.* ; Ricci, A.* ; Theis, F.J. ; Bittner, S.* ; Gökçe, A.* ; Peters, A.* ; Liesz, A.*

T cells modulate the microglial response to brain ischemia.

eLife 11:e82031 (2022)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Neuroinflammation after stroke is characterized by the activation of resident microglia and the invasion of circulating leukocytes into the brain. Although lymphocytes infiltrate the brain in small number, they have been consistently demonstrated to be the most potent leukocyte subpopulation contributing to secondary inflammatory brain injury. However, the exact mechanism of how this minimal number of lymphocytes can profoundly affect stroke outcome is still largely elusive. Here, using a mouse model for ischemic stroke, we demonstrated that early activation of microglia in response to stroke is differentially regulated by distinct T cell subpopulations - with TH1 cells inducing a type I INF signaling in microglia and regulatory T cells (TREG) cells promoting microglial genes associated with chemotaxis. Acute treatment with engineered T cells overexpressing IL-10 administered into the cisterna magna after stroke induces a switch of microglial gene expression to a profile associated with pro-regenerative functions. Whereas microglia polarization by T cell subsets did not affect the acute development of the infarct volume, these findings substantiate the role of T cells in stroke by polarizing the microglial phenotype. Targeting T cell-microglia interactions can have direct translational relevance for further development of immune-targeted therapies for stroke and other neuroinflammatory conditions.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords T Cells ; Immunology ; Inflammation ; Microglia ; Mouse ; Neuroscience ; Single-cell Transcriptomics ; Stroke; B-cells; Stroke; Neuroinflammation; Differentiation; Inflammation; Mechanisms; Expression; Cytokine; Invasion
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 11, Issue: , Pages: , Article Number: e82031 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Institute of Diabetes and Regeneration Research (IDR)
Grants European Research Council