科研之友
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摘要
BackgroundCerebral microbleeds (CMBs) are an early sign of many neurological disorders and accompanied by local neuroinflammation and brain damage. As important regulators of immune response and neuroinflammation, the biological behavior and role of gamma delta T cells after CMBs remain largely unknown. MethodsWe made a spot injury of microvessel in the somatosensory cortex to mimic the model of CMBs by two-photon laser and in vivo tracked dynamical behaviors of gamma delta T cells induced by CMBs using TCR-delta(GFP) transgenic mice. Biological features of gamma delta T cells in the peri-CMBs parenchyma were decoded by flow cytometry and Raman spectra. In wildtype and gamma delta T cell-deficient mice, neuroinflammation and neurite degeneration in the peri-CMBs cortex were studied by RNAseq, immunostaining and in vivo imaging respectively. ResultsAfter CMBs, gamma delta T cells in the dural vessels were tracked to cross the meningeal structure and invade the brain parenchyma in a few days, where the division process of gamma delta T cells were captured. Parenchymal gamma delta T cells were highly expressed by CXCR6 and CCR6, similar to meningeal gamma delta T cells, positive for IL-17A and Ki67 (more than 98%), and they contained abundant substances for energy metabolism and nucleic acid synthesis. In gamma delta T cell-deficient mice, cortical samples showed the upregulation of neuroinflammatory signaling pathways, enhanced glial response and M1 microglial polarization, and earlier neuronal degeneration in the peri-CMBs brain parenchyma compared with wildtype mice. ConclusionCMBs induce the accumulation and local proliferation of gamma delta T cells in the brain parenchyma, and gamma delta T cells exert anti-neuroinflammatory and neuroprotective effects at the early stage of CMBs.
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单位1; 南通大学; 中国科学院; 广东工业大学
