IL-34 attenuates acute T cell-mediated rejection following renal transplantation by upregulating M2 macrophages polarization

Published: 21 September 2023| Version 1 | DOI: 10.17632/bmgx9pnrrg.1
Bin Ni


Objective: To investigate the role of IL-34 in acute T cell-mediated rejection (TCMR) after kidney transplantation. Methods: The mice acute TCMR model of renal transplantation was established and identified by HE and IHC staining. Then, IHC staining of IL-34 was also performed to determine the expression of IL-34 in allografts. Recipients were infected with IL-34 overexpression adeno-associated virus, infection efficiency of which was estimated by ELISA, WB, and immunofluorescence. HE and IHC staining were used to estimate the grades of TCMR. Flow cytometry was performed on lymphocytes in spleens of recipients including Tregs and M2 macrophages. The expression of cytokines in vivo was analyzed by Mouse Cytokine Grp I Panel. Finally, Tregs and M2 macrophages were cultured in vitro and treated with IL-34 to observe the effects of IL-34 on the differentiation of the cells. Results: The mouse TCMR model was successfully established by HE, PAS, CD4 and CD8 IHC staining. The expression of IL-34 was significantly decreased in allografts with TCMR. BALB/c mice were successfully infected with IL-34 overexpression adeno-associated virus. Subsequently, the grade of rejection in mice TCMR model was evaluated by HE and IHC staining according to Banff criteria. It is suggested that the grade of TCMR in IL-34 overexpressed mice was significantly decreased. IHC staining and Flow cytometry showed that the proportion of Tregs and M2 macrophages in the spleens and allografts were significantly increased in IL-34 overexpressed mice. Serum levels of IFN- γ, IL-17 and TNF-α were downregulated in IL-34 overexpressed mice. Moreover, IL-34 could promote macrophage M2 polarization, while failed to promote differentiation of naïve T cells into Tregs in vitro. Conclusion: Overexpression of IL-34 may attenuate the progression of TCMR episodes in allografts by increasing the polarization of M2 macrophages in the spleens and allografts, which may become a potential therapeutic strategy for TCMR. Keywords: Kidney transplantation; T cell-mediated rejection; IL-34; M2 macrophage



Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital


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