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

Abstract

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.

The Role of the Blood Neutrophil-to-Lymphocyte Ratio in Aneurysmal Subarachnoid Hemorrhage

“…Neuroinflammation is prevalent in these conditions and plays with similar mechanisms. In the early stage of both SAH and AIS, the activation of microglia by neutrophil is vital for following cascade of inflammation, with similar inflammatory mediators and pathways (120). Moreover, Tregs also play a major role in immunomodulatory function and neuroprotection after AIS (121).…”

“…In the early stage of both SAH and AIS, the activation of microglia by neutrophil is vital for following cascade of inflammation, with similar inflammatory mediators and pathways ( 120 ). Moreover, Tregs also play a major role in immunomodulatory function and neuroprotection after AIS ( 121 ). Valuable findings and breakthroughs may occur through comparing the similarities and differences of pathophysiological mechanisms about neuroinflammation among these medical conditions.…”

Ischemic stroke: From pathological mechanisms to neuroprotective strategies

“…Compared to other T cells, mucosal-associated invariant T (MAIT) cells were involved earlier in neuroinflammation after stroke. TMCAO mice with a MAIT deficiency or MAIT inhibitory ligand drugs (isobutyryl 6-formylpterin, i6-FP, in Table 1 ) showed a smaller infarct size compared to the model group ( 89 ). NKT cells are also part of non-specific immune T cells.…”

MAITabolism2 – the emerging understanding of MAIT cell metabolism and their role in metabolic disease

“…This study proposes circulating cell frequency as a marker for CMD progression ( 58 ). On the contrary, inhibition of MAIT cells was found to be neuroprotective in the model of ischemic brain injury as MAIT cell cytokines were found to cause neuroinflammation following ischemic reperfusion ( 67 ).…”