Project description:The existence of immunoregulatory mechanisms that control autoimmunity in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we found that psoriasis is tightly associated with a significant downregulation of fatty acid metabolism and biosynthesis pathways as well as Th2 signature genes. Among lipids-activated transcription factors, LXR and PPAR were required for fatty acid homeostasis and resistance to psoriasis in mice. STAT6 played a role in the homeostatic expression of LXR and PPARγ in the skin. Additionally, innate lymphoid cells established tonic type 2 immunity in normal skin by producing IL-13 continually. Mice lacking tonic type 2 immunity were more susceptible to psoriatic inflammation in vivo. In human skin, inhibiting tonic type 2 immunity worsened psoriasis-like inflammation and IL-17 production, while activating LXR or PPAR inhibited them. Therefore, tonic type 2 immunity is an essential tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.
Project description:PGLYRP1 is highly co-expressed with known co-inhibitory molecules and might be a promising novel target for immunotherapy. Indeed, genetic deletion of PGLYRP1 in mice led to decreased tumor growth and an increased activation/effector phenotype in CD8+ T cells, suggesting an inhibitory function of PGLYRP1 in CD8+ T cells. Surprisingly, genetic deletion of PGLYRP1 strongly protected against experimental autoimmune encephalomyelitis (EAE), a model of autoimmune disease in the central nervous system (CNS). Pglyrp1-deficient myeloid cells had a defect in antigen-presentation and T cell activation, indicating that PGLYRP1 might act as a proinflammatory molecule in myeloid cells during autoimmunity. Our results highlight PGLYRP1 as a promising novel target for immunotherapy, that, when targeted, elicits a potent anti-tumor immune response while protecting against tissue inflammation and autoimmunity.
Project description:Targeting cathepsin B by cycloastragenol enhances anti-tumor immunity via inhibiting MHC-1 degradation and promoting the presentation of tumor antigen
Project description:Purpose:We want to elaborate the specific mechanism of CAG inhibiting the growth of transplanted mouse colon cancer cell MC38. Methods:After MC38 cells were inoculated into C57BL/6 mice for 6 days, the mice were evenly divided into PBS group and CAG group, and PBS and CAG (50mg / kg) were administered by gavage every day. On the 18th day, the mouse tumors were removed, and one tumor was selected to prepare single cell suspension for 10x-scRNA-seq and 10x-scATAC-seq. Results:We found that CAG promoted the antigen-presenting function of tumor cells and enhanced the killing ability of CD8 T cells. Conclusions:CAG enhances the antitumor immunity of CD8 T cells by promoting the antigen presentation of tumor cells.
Project description:Purpose:We want to elaborate the specific mechanism of CAG inhibiting the growth of transplanted mouse colon cancer cell MC38. Methods:After MC38 cells were inoculated into C57BL/6 mice for 6 days, the mice were evenly divided into PBS group and CAG group, and PBS and CAG (50mg / kg) were administered by gavage every day. On the 18th day, the mouse tumors were removed, and one tumor was selected to prepare single cell suspension for 10x-scRNA-seq and 10x-scATAC-seq. Results:We found that CAG promoted the antigen-presenting function of tumor cells and enhanced the killing ability of CD8 T cells. Conclusions:CAG enhances the antitumor immunity of CD8 T cells by promoting the antigen presentation of tumor cells.