T cells modulate the microglial response to brain ischemia

Corinne Benakis, Alba Simats, Sophie Tritschler, Steffanie Heindl, Simon Besson-Girard, Gemma Llovera, Kelsey Pinkham, Anna Kolz, Alessio Ricci, Fabian J. Theis, Stefan Bittner, Özgün Gökce, Anneli Peters, Arthur Liesz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 subpop-ulation 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.

Original languageEnglish
Article numbere82031
JournaleLife
Volume11
DOIs
StatePublished - Dec 2022
Externally publishedYes

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