’Sialophorin is an essential element for fungal vaccine induced Tc17 cell differentiation and viability’ 2666

Abstract Description Costimulatory molecules are integral for shaping T-cell responses and are attractive targets for T-cell modulation. Sialophorin (CD43) has disparate functions in hematopoietic cells and has been shown to negatively regulate antiviral CD8+ T cell responses. We investigated the mechanisms of essential role of CD43 for potentiating fungal vaccine responses. Using a mouse model of vaccine immunity, we demonstrated that CD43 significantly enhances Tc17 cell responses and fungal immunity. Our findings reveal that CD43 activates the Akt-mTOR-HIF1α signaling pathway, leading to increased RORγt expression in Tc17 cells without affecting their proliferation. Inhibition of Akt, mTORC1, or HIF1α resulted in diminished effector CD8+ T cell responses, while HIF1α stabilization augmented Tc17 responses in a CD43-dependent manner. Adoptive transfer experiments revealed the role of CD43 for effector CD8+ T cell survival by upregulating Bcl-2 levels and suppressing Caspase-3 activation. Notably, the Caspase-3 inhibitor treatment improved the survival of CD43-deficient Tc17 cells. These results offer a new perspective on CD43’s function, revealing its positive regulatory role in T-cell responses within the context of Tc17 cells and fungal immunity. Our study identifies CD43 as a potential target for enhancing vaccine efficacy and bolstering immunity against pulmonary fungal infections, offering new avenues for immune prophylactic/therapeutic interventions. Funding Sources This work is supported by NIH-NIAID 5R01AI153522 (to SGN). Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)