Mucosal‐Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation

Autor: Sho Nakajima, Ryota Tanaka, Kazuo Yamashiro, Asako Chiba, Daisuke Noto, Toshiki Inaba, Naohide Kurita, Nobukazu Miyamoto, Takuma Kuroki, Hideki Shimura, Yuji Ueno, Takao Urabe, Sachiko Miyake, Nobutaka Hattori
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 7 (2021)
Druh dokumentu: article
ISSN: 2047-9980
DOI: 10.1161/JAHA.120.018803
Popis: Background Mucosal‐associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. Methods and Results We used MR1 knockout C57BL/6 (MR1−/−) mice and wild‐type littermates (MR1+/+). After performing a transient middle cerebral artery occlusion (tMCAO), we evaluated the association with inflammation and prognosis in the acute cerebral ischemia. Furthermore, we analyzed the tMCAO C57BL/6 mice administered with the suppressive MR1 ligand and the vehicle control. We also evaluated the infiltration of MAIT cells into the ischemic brain by flow cytometry. Results showed a reduction of infarct volume and an improvement of neurological impairment in MR1−/− mice (n=8). There was a reduction in the number of infiltrating microglia/macrophages (n=3–5) and in their activation (n=5) in the peri‐infarct area of MR1−/− mice. The cytokine levels of interleukin‐6 and interleukin‐17 at 24 hours after tMCAO (n=3–5), and for interleukin‐17 at 72 hours after tMCAO (n=5), were lower in the MR1−/− mice. The administration of the suppressive MR1 ligand reduced the infarct volume and improved functional impairment (n=5). Flow cytometric analysis demonstrated there was a reduction of MAIT cells infiltrating into the ischemic brain at 24 hours after tMCAO (n=17). Conclusions Our results showed that MAIT cells play an important role in neuroinflammation after focal cerebral ischemia and the use of MAIT cell regulation has a potential role as a novel neuroprotectant for the treatment of acute ischemic stroke.
Databáze: Directory of Open Access Journals
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