Death-associated protein kinase 1 (DAPK1) controls CD8 T cell activation, trafficking, and antitumor activity.

Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K-Akt in CD8 T cell mTORC1 activation, a link between Akt-mTORC1 signaling and CD8 trafficking has been demonstrated. We have recently discovered that TCR-induced calcineurin activates DAPK1, which interacts with TSC2 via its death domain and phosphorylates TSC2 via its kinase domain to mediate mTORC1 activation in CD8 T cells.

DAPK1 (death associated protein kinase 1) mediates mTORC1 activation and antiviral activities in CD8 T cells.

Mechanistic target of rapamycin complex 1 (mTORC1) regulates CD8 T-cell differentiation and function. Despite the links between PI3K-AKT and mTORC1 activation in CD8 T cells, the molecular mechanism underlying mTORC1 activation remains unclear. Here, we show that both the kinase activity and the death domain of DAPK1 are required for maximal mTOR activation and CD8 T-cell function.

The macrophage-specific V-ATPase subunit ATP6V0D2 restricts inflammasome activation and bacterial infection by facilitating autophagosome-lysosome fusion.

Macroautophagy/autophagy is a conserved ubiquitous pathway that performs diverse roles in health and disease. Although many key, widely expressed proteins that regulate autophagosome formation followed by lysosomal fusion have been identified, the possibilities of cell-specific elements that contribute to the autophagy fusion machinery have not been explored. Here we show that a macrophage-specific isoform of the vacuolar ATPase protein ATP6V0D2/subunit d2 is dispensable for lysosome acidification, but promotes the completion of autophagy via promotion of autophagosome-lysosome fusion through its interaction with STX17 and VAMP8.

Transcriptional Regulation of T Cell Metabolism Reprograming.

T cell activation, differentiation, and function are tightly regulated by a complex network of transcription factors, epigenetic modifications, and signaling pathways of both TCR and cytokines. Over the past decade, it is increasingly clear that T cell immune responses are also regulated by their associated metabolic reprograming. Compared with relatively well-understood transcriptional regulation of T cell activation, differentiation, and function, less is known about the transcriptional regulation of T cell metabolic reprograming during T cell immune responses.

α-Lactose Improves the Survival of Septic Mice by Blockade of TIM-3 Signaling to Prevent NKT Cell Apoptosis and Attenuate Cytokine Storm.

Sepsis is the leading cause of death among critically ill patients and natural killer T (NKT) cell activation is essential to induce inflammatory cytokine cascade in sepsis. However, little is known about what regulates the NKT cell function during sepsis. Herein, we showed that T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in NKT cells is elevated in experimental mice during sepsis.