M-CSF and prostratin induced Mregs promote immune tolerance in transplanted mice through Arg-1 pathway.

Regulatory macrophages (Mregs) are a group of heterogeneous macrophages. These cells could induce immunosuppressive effects through the expression of immune regulatory molecules and cytokines. The differentiation of Mregs was induced by treating bone marrow cells with M-CSF and prostratin in vitro. The cell-phenotypes and immunosuppressive function were determined by flow cytometry. Rt-PCR was employed to assess the mechanisms of Mregs. Skin grafted mouse model was used for in vivo validation. Mregs induced by M-CSF + prostratin had a strong inhibitory effect on T cell proliferation and cytokines production. The phenotype of induced bone marrow cells changed towards Mregs. These Mregs could induce the differentiation of Tregs in vivo. Arg-1 expression in these cells were significantly upregulated. Inhibition of arginase (Arg) or arginine supplement significantly reversed the immunosuppressive function. In mice skin-grafted models, adoptive transfer of these Mregs significantly prolonged allograft survival. In mice models, Arg-1 expression significantly elevated on skin grafts cells and Tregs increased in graft tissues. We successfully developed a Mregs-inducing protocol with the combination of M-CSF and prostratin in vitro. M-CSF + prostratin induced Mregs prevented mice skin graft rejection through upregulating the expression Arg-1. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Jiawei Ji, Yuan Zhuang, Haozhou Wang, Chang Feng, Yong Zhao, Xiaodong Zhang. M-CSF and prostratin induced Mregs promote immune tolerance in transplanted mice through Arg-1 pathway. International immunopharmacology. 2021 Oct;99:108014

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PMID: 34332340

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