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. Tumor necrosis factor α (TNF-α)-induced protein 8 like-1 (TIPE1), a new member of the tumor necrosis factor α-induced protein 8 family, may be related to cell death. The aim of the present study was to elucidate the effect of TIPE1 on the 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. In vitro, we found that expression of CD80, CD86, and major histocompatibility complex class II in DCs and levels of cytokines, including tumor necrosis factor α and interleukin 12p40, were elevated; similarly, T-cell proliferation and differentiation were promoted when the gene expressing TIPE1 was silenced. Next, we examined the in vivo role of TIPE1 in a cecal ligation and puncture animal model system. Flow cytometry of the immune functional status in DCs revealed negative regulation of TIPE1 on DC maturation, as well as activation. Moreover, changes in PD-L1/PD-1 levels confirmed the negative effect of TIPE1 in DCs. Collectively, we report that TIPE1 might exert negative regulation in sepsis, at least in part by inhibiting DC maturation and subsequent T-cell-mediated immunity via PD-L1/PD-1 signaling.