BackgroundEvidence suggests that brain infiltration of lymphocytes contributes to acute neural injury after cerebral ischemia. However, the spatio-temporal dynamics of brain-infiltrating lymphocytes during the late stage after cerebral ischemia remains unclear.MethodsC57BL/6 (B6) mice were subjected to sham, photothrombosis, or 60-min transient middle cerebral artery occlusion (MCAO) procedures. Infarct volume, neurodeficits, production of reactive oxygen species (ROS) and inflammatory factors, brain-infiltrating lymphocytes, and their activation as well as pro-inflammatory cytokine IFN-γ production were assessed. Brain-infiltrating lymphocytes were also measured in tissue sections from post-mortem patients after ischemic stroke by immunostaining.ResultsIn mice subjected to transient MCAO or photothrombotic stroke, we found that lymphocyte infiltration persists in the ischemic brain until at least day 14 after surgery, during which brain infarct volume significantly diminished. These brain-infiltrating lymphocytes express activation marker CD69 and produce proinflammatory cytokines such as IFN-γ, accompanied with a sustained increase of reactive oxygen species (ROS) and inflammatory cytokines release in the brain. In addition, brain-infiltrating lymphocytes were observed in post-mortem brain sections from patients during the late stage of ischemic stroke.ConclusionOur results demonstrate that brain-infiltration of lymphocytes persists after the acute stage of cerebral ischemia, facilitating future advanced studies to reveal the precise role of lymphocytes during late stage of stroke.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1017-0) contains supplementary material, which is available to authorized users.
In this study, we strove to substantiate the ability of linc-MAF-4 to act as a regulator of pathogenesis during multiple sclerosis (MS). We recruited 34 patients who were diagnosed with MS according to the revised McDonald criteria. Six patients with MS and 5 healthy volunteers contributed peripheral blood mononuclear cells for microarray analysis. Subsequent knockdown and overexpression of linc-MAF-4 in naive CD4 T cells from the additional 28 patients with MS was performed to track changes in CD4 T-cell subsets and their function, as well as to confirm results from the prior microarray analysis. Expression of linc-MAF-4 increased significantly in peripheral blood mononuclear cells of patients with MS compared with those of control participants. In addition, linc-MAF-4 regulated encephalitogenic T helper (T)1-cell differentiation in patients with MS. Transfection of synthetic linc-MAF-4 into naive CD4 T cells facilitated T1-cell differentiation and inhibited T2-cell differentiation by directly inhibiting MAF, which is a T2-cell transcription factor. Linc-MAF-4 also promoted activation of CD4 T cells from patients with MS. Expression level of linc-MAF-4 correlated with the annual relapse rate in patients with MS. Our results suggest that linc-MAF-4 is involved in the pathogenesis of MS, specifically via regulation of encephalitogenic T cells.-Zhang, F., Liu, G., Wei, C., Gao, C., Hao, J. Linc-MAF-4 regulates T1/T2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF.
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