Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain.

Daniel Manrique-Castano, Egor Dzyubenko, Mina Borbor, Paraskevi Vasileiadou, Christoph Kleinschnitz, Lars Roll, Andreas Faissner, Dirk M Hermann

Brain, behavior, and immunity 2021 Jan

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As an endogenous activator of toll-like receptor-4 (Tlr4), the extracellular matrix glycoprotein tenascin-C (TnC) regulates chemotaxis, phagocytosis and proinflammatory cytokine production in microglia. The role of TnC for ischemic brain injury, post-ischemic immune responses and stroke recovery has still not been evaluated. By comparing wild type and TnC-/- mice exposed to transient intraluminal middle cerebral artery occlusion (MCAO), we examined the effects of TnC deficiency for ischemic injury, neurological deficits, microglia/macrophage activation and brain leukocyte infiltration using behavioural tests, histochemical studies, Western blot, polymerase chain reaction and flow cytometry. Histochemical studies revealed that TnC was de novo expressed in the ischemic striatum, which contained the infarct core, and overlapped with the area of strongest accumulation of Iba1 + microglia/macrophages. TnC deficiency increased overall Iba1 immunoreactivity in the perilesional cortex, suggesting that TnC might restrict the distribution of microglial cells to the infarct core. By analysing microglial morphology in 3D we found that the post-ischemic loss of microglial cell territory, branching and volume at 3 and 7 days post-ischemia was amplified in the brains of TnC deficient compared with wild type mice. Microglial cell number was not different between genotypes. Hence, TnC deficiency reduced tissue surveillance by microglial cells. Concomitantly, the number of infiltrating leukocytes and, more specifically, T cells was increased in the ischemic brain parenchyma of TnC deficient compared with wild type mice. Ischemic injury and neurological deficits were not affected by TnC deficiency. We propose that the reduced microglia surveillance in TnC deficient mice might favour leukocyte accumulation in the ischemic brain. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Daniel Manrique-Castano, Egor Dzyubenko, Mina Borbor, Paraskevi Vasileiadou, Christoph Kleinschnitz, Lars Roll, Andreas Faissner, Dirk M Hermann. Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain. Brain, behavior, and immunity. 2021 Jan;91:639-648