Abstract T P202: Crosstalk Between Microglia and T Cells Mediated by FasL After Cerebral Ischemia
Background: Inflammation is closely implicated in the pathogenesis and outcome of ischemic stroke. Although crosstalk between microglia and T cells has been studied in CNS diseases such as Parkinson’s disease, yet few research has focused this relationship on stroke, and no definite mechanism has been proposed to explain the relationship. In this study, we discussed the crosstalk between microglia and T cells and the probable role of FasL in the progress.
Methods: Primary microglia were extracted from the cortexes of new born C57BL/6J (B6) mice while primary T cells were extracted from spleens of adult B6 mice. MCAO and OGD model were used to mimic cerebral ischemic injury in vivo and in vitro respectively. T cell chemotaxis assay was determined by transwell system. Cell markers in vivo were detected by immunofluorescence. The expression of cytokines were detected by Q-PCR. The amount of soluble FasL into the cultured media were measured by ELISA.
Results: In vivo, T cells infiltrated into the ischemic lesions and aggregated around microglia within 24 h after MCAO. The expression of FasL in microglia was also up-regulated after MCAO. However, in FasL mutant (Gld) mice, the infiltration and aggregation of T cells were induced. In vitro, when coculturing primary T cells with primary microglia, crosstalk also existed between them morphologically after OGD. Furthermore, proinflammatory cytokines such as IL-1β, IL-6 were increased and anti-inflammatroy cytokines such as IL-10 were reduced by Q-PCR. However, the crosstalk wasn’t obvious in Gld primary cocultured cells. On the other hand, soluble FasL was increased in the supernatant of activated microglia by ELISA. In chemotaxis assay, T cells were chemotactic to supernatant of activated microglia while the effect was weakened after inhibiting FasL or MCP-1, which indicating that soluble FasL released by microglia may also play an important role in chemoattracting T cells.
Conclusions: These data suggest that an inflammatory crosstalk take place between activated microglia and T cells after cerebral ischemia, in which FasL may play an important part. Microglia may chemoattract periphery T cells by releasing soluble FasL after ischemic injury.
Author Disclosures: D. Ye: None. X. Chen: None. Y. Xu: None.
- © 2014 by American Heart Association, Inc.