Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Objective: To explore the effect of Batf and IRF1 on IL-10/IL-27 expression in DCs during transplant tolerance induction.
Methods: Allogeneic heart transplants were performed between WT and Batf ko or IRF1ko mice, to test the effect of IRF1 and Batf on graft survival and graft infiltrating lymphocytes. In vitro, we generated WT, Batf1ko and IRF1ko 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. Finally, we adoptively transferred the stimulated BM-DC into allogeneic heart transplant mice (intravenously) to induce tolerance. Concurrently, we checked the graft survival and graft infiltrating lymphocytes. 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, Batf ko and IRF1ko mice could shorten the graft survival, and graft infiltrating T cells in Batf ko and IRF1ko mice group expressed less IL-10 and Foxp3, but more IFN-g. In vitro, Batf ko and IRF1ko BM-DC expressed higher amounts of CD80, CD86 and MHC class II and secreted less IL-27 and IL-10 as checked by ELISA after 100ng/ml LPS stimulation. Moreover, they could inhibit T cells to express IL-10 in a co-culture experiment. In a BM-DC adoptive experiment, Batf ko and IRF1ko BM-DC could inhibit the progress of tolerance and ex vivo analysis showed that T cells could express less IL-10 in Batf ko and IRF1ko BM-DC group.At last, we found that Batf and IRF1 could induce IL-27 and IL-10 expression as determined by a Luciferase Reporter Assay. IRF1 and BATF bind to IL-27 and IL-10 promoter by Chip-PCR.
Conclusion: IRF1 and Batf could bind to IL-27/IL-10 promoter, induce IL-27/IL-10 expression, and then inhibit T cell response and induce transplant tolerance.
CITATION INFORMATION: Gu G, Hang H, Xia Q. The Transcription Factor Batf and IRF1 Controls IL-10/IL-27 Expression in Dendritic Cells and Transplant Tolerance Induction. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Gu G, Hang H, Xia Q. The Transcription Factor Batf and IRF1 Controls IL-10/IL-27 Expression in Dendritic Cells and Transplant Tolerance Induction. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/the-transcription-factor-batf-and-irf1-controls-il-10il-27-expression-in-dendritic-cells-and-transplant-tolerance-induction/. Accessed March 26, 2019.
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