Effect of TIPE1 on immune function of dendritic cells and its signaling pathway in septic mice.

Dendritic cell (DC) dysfunction plays a pivotal role in sepsis-induced immunosuppression. TIPE1, a new member of the TNFAIP8 (tumor necrosis factor-α-induced protein 8) family, may be related to cell death. The aim of present study was to elucidate the effect of TIPE1 on immune function of DCs and its regulatory mechanism via PD-L1/PD-1 signaling in mice. Sepsis was induced in adult C57BL/6 male mice via cecal ligation and puncture (CLP). In vitro, we found that expressions of CD80, CD86, MHC-II in DCs, and cytokines including TNF-α as well as IL-12p40 levels were elevated, similarly, T-cell proliferation and differentiation were promoted when TIPE1 gene was silenced. Next, we examined the in vivo role of TIPE1 in a CLP animal model system. Flow cytometric analysis of the immune functional status in DCs revealed negative regulation of TIPE1 on DC maturation as well as activation. Moreover, changes of PD-L1/PD-1 levels confirmed such a negative effect of TIPE1 in DCs. Collectively, we report that TIPE1 might exert a negative regulation in sepsis, at least in part, by inhibiting DC maturation and subsequent T-cell mediated immunity via PD-L1/PD-1 signaling.