*Purpose: Acute and chronic rejection are key problems in renal transplantation. It is ideal to induce immune tolerance to suppress rejection while regulatory macrophages (Mregs) which play critical roles are one of the approaches against rejection. Little do scientists know about how to further improve and establish the Mregs with powerful immunosuppressive function.

*Methods: To solve this problem, we induced regulatory macrophages derived from BALB/c bone marrow through various cytokines in vitro. Cell phenotype was analyzed by flow cytometry. ConA stimulated T cell proliferation assay was used to evaluate Mregs inhibitory function. RNA-seq revealed immunosuppressive molecules that regulate the functioning of regulatory macrophages. RT-PCR and flow cytometry were used to further validate the identified immunosuppressive molecules.

*Results: The results indicated that macrophages induced by IL-33 showed the characteristics of Mregs, which significantly inhibited the proliferation of T cells and promoted the high expression of Foxp3 in CD4+ T cells. Moreover, Mregs induced by IL-33 exert immunosuppressive function mainly through siglec-10.

*Conclusions: Our study optimized the amplification system of Mregs induced by IL-33 in vitro and clarified systematically the characteristics of the gene expression profile of Mregs induced by IL-33 and the cellular and molecular mechanisms in the establishment of transplant immune tolerance. In summary, our study provides a strategy for the construction of immunosuppressive Mregs and comes up with a novel method to ameliorate rejection after renal transplantation.

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