Oral tolerance has been implicated in the protection of transplant rejection in the animal models. Antigen presenting cells (APCs) are responsible for sampling their environment for antigens and information about the integrity of the immune system. However, the role of APC in oral tolerance is not fully clear. Here, our results showed that oral tolerance could be induced by administrating anti-CD3 antibody, which in turn could prolong the allograft survival in mouse heart transplantation model. Foxp3+ and IL-10+ T cells were highly expressed in the allograft infiltrating lymphocytes. RNA-seq results showed the DC expressed more tolerogenic genes such as IL27, IL10, Tim3 and so on. To test the function of dendritic cell subsets, we transient depletion of target target APC subsets by injection DT in BDCA2-DTR, zDC-DTR and CD11c-DTR mice during oral tolerance induction. Results showed that temporary depletion of conventional DCs could not prolong the allograft survival in zDC-DTR mice, and no difference of Foxp3+ and IL-10+ T cells were found in the allograft infiltrating lymphocytes compared to the PBS control. In vitro DC and T cells co-culture experiment results showed cDC could induce more IL10+ T cells. Finally, IL27 was found to be highly expressed in cDCs of oral tolerant mice. Oral tolerance could not be induced and allograft survival could not be prolonged in IL27R knockout mice. Based on our findings, oral tolerance may protect cardiac transplant rejection by promoting the expression of IL27 in cDC that regulate type 1 regulatory T cell function.

CITATION INFORMATION: Gu G., Lu T., Xu N., Xia Q. Influence of Dendritic Cell Subsets on Enhancing Oral Tolerance in Cardiac Transplantation Model Am J Transplant. 2017;17 (suppl 3).

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