Objective: To explore the effect of Bat3 on DCs during transplant tolerance induction.

Methods: Allogeneic heart transplants were performed between WT and Bat3flox/floxCD11c-Cre+ mice, to test the effect of Bat3 on graft survival and graft infiltrating lymphocytes. In vitro, we generated WT and Bat3cko bone marrow derived dendritic cells (BM-DC), and then tested their expression of co-stimulatory molecules, cytokine production and the function on T cells after LPS stimulation. Furthermore, we tested the effect of Bat3 on IL-27/IL-10 expression using a luciferase reporter assay and Chip-PCR.

Results

In murine heart transplant models, Bat3cko mice could prolong the graft survival, and graft infiltrating T cells in Bat3cko mice group expressed more IL-10 and Foxp3, but less IFN-g and IL-17. The RNA-seq of graft infiltrating T cells showed that T cells in Bat3cko mice group expressed a more-tolerant phenotype. In vitro, Bat3cko BM-DC expressed lower amounts of CD80, CD86 and MHC class II and secreted more IL-27 and IL-10 as checked by ELISA after 100ng/ml LPS stimulation. Moreover, they could induce T cells to express more IL-10 in a co-culture experiment. At last, we found that Bat3 could inhibit IRF1-induced IL-27 and IL-10 expression as determined by a Luciferase Reporter Assay. The bindings of IRF1 to IL-27 and IL-10 promoter were enhanced in Bat3cko BM-DC as we found using Chip-PCR. Co-IP experiments showed that Bat3 could bind to IRF1.

Conclusion

Bat3 could bind to IRF1. Loss of Bat3 on DC could increase IL-27/IL-10 expression, and then inhibit T cell response and induce transplant tolerance.

CITATION INFORMATION: Gu G, Hang H, Xia Q. Blocked of Bat3 Expression Promotes Transplant Tolerance by Inducing IL-10 Expression in Dendritic Cells. Am J Transplant. 2017;17 (suppl 3).

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