Myeloid GSDMD regulates T cell responses in AD

Gasdermin D (GSDMD) -mediated pyroptosis has been associated with Alzheimer's disease (AD), but the effect of GSDMD upon peripheral and central nervous system AD immune responses has not been well characterized. Herein, we found that GSDMD was activated by caspases in both the AD spleen and brain during disease progression. Loss of myeloid cell GSDMD was shown to impair effector T cell immune response in the periphery and prevent T cell infiltration into brain, especially CD8 T cells, with an overall reduction in neuro-inflammation. RNA-seq was performed on splenocytes of myeloid cell-conditional GSDMD-depleted 5XFAD mice and littermate controls to explore the mechanism of GSDMD regulating T cell responses in AD.