IL-34 Attenuates Acute T Cell-mediated Rejection Following Renal Transplantation by Upregulating M2 Macrophages Polarization

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Jan 17

PMID 38230243

Authors

Bin Ni

Dongliang Zhang

Hai Zhou

Ming Zheng

Zijie Wang

Jun Tao

Zhijian Han

Xiaobin Ju

Ruoyun Tan

Min Gu

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the role of Interleukin-34 (IL-34) in acute T cell-mediated rejection (TCMR) following renal transplantation.

Methods: The mice acute TCMR model of renal transplantation was established and identified by hematoxylin and eosin (HE) and immunohistochemistry (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 enzyme linked immunosorbent assay (ELISA), Western blot, 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 regulatory T cells (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 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, periodic acid shiff (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 interferon-gamma (IFN-γ), IL-17 and tumor necrosis factor-alpha (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 .

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.

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References

Yin D, Fu J, Chen R, Shushakova N, Allabauer I, Wei X . A Modified Surgical Technique for Kidney Transplantation in Mice. J Vis Exp. 2022; (185). DOI: 10.3791/63434. View

Van Raemdonck K, Umar S, Palasiewicz K, Volin M, Elshabrawy H, Romay B . Interleukin-34 Reprograms Glycolytic and Osteoclastic Rheumatoid Arthritis Macrophages via Syndecan 1 and Macrophage Colony-Stimulating Factor Receptor. Arthritis Rheumatol. 2021; 73(11):2003-2014. PMC: 8568622. DOI: 10.1002/art.41792. View

San Segundo D, Ruiz P, Irure J, Arias-Loste M, Cuadrado A, Puente A . Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation. Transplant Proc. 2016; 48(9):2977-2979. DOI: 10.1016/j.transproceed.2016.08.038. View

Greter M, Lelios I, Pelczar P, Hoeffel G, Price J, Leboeuf M . Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia. Immunity. 2012; 37(6):1050-1060. PMC: 4291117. DOI: 10.1016/j.immuni.2012.11.001. View

Bezie S, Freuchet A, Serazin C, Salama A, Vimond N, Anegon I . IL-34 Actions on FOXP3 Tregs and CD14 Monocytes Control Human Graft Rejection. Front Immunol. 2020; 11:1496. PMC: 7431608. DOI: 10.3389/fimmu.2020.01496. View

Guillonneau C, Bezie S, Anegon I . Immunoregulatory properties of the cytokine IL-34. Cell Mol Life Sci. 2017; 74(14):2569-2586. PMC: 11107603. DOI: 10.1007/s00018-017-2482-4. View

Zhao Z, Pan G, Tang C, Li Z, Zheng D, Wei X . IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer Cell M2 Polarization. Transplantation. 2018; 102(6):e265-e274. DOI: 10.1097/TP.0000000000002194. View

Wada Y, Gonzalez-Sanchez H, Weinmann-Menke J, Iwata Y, Ajay A, Meineck M . IL-34-Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL- Mice. J Am Soc Nephrol. 2019; 30(2):244-259. PMC: 6362618. DOI: 10.1681/ASN.2018090901. View

Sawitzki B, Harden P, Reinke P, Moreau A, Hutchinson J, Game D . Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020; 395(10237):1627-1639. PMC: 7613154. DOI: 10.1016/S0140-6736(20)30167-7. View

10.

Wang Y, Szretter K, Vermi W, Gilfillan S, Rossini C, Cella M . IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat Immunol. 2012; 13(8):753-60. PMC: 3941469. DOI: 10.1038/ni.2360. View

11.

Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M . The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020; 20(9):2318-2331. PMC: 7496245. DOI: 10.1111/ajt.15898. View

12.

Landwehr-Kenzel S, Zobel A, Hoffmann H, Landwehr N, Schmueck-Henneresse M, Schachtner T . Ex vivo expanded natural regulatory T cells from patients with end-stage renal disease or kidney transplantation are useful for autologous cell therapy. Kidney Int. 2018; 93(6):1452-1464. DOI: 10.1016/j.kint.2018.01.021. View

13.

Nandi S, Cioce M, Yeung Y, Nieves E, Tesfa L, Lin H . Receptor-type protein-tyrosine phosphatase ζ is a functional receptor for interleukin-34. J Biol Chem. 2013; 288(30):21972-86. PMC: 3724651. DOI: 10.1074/jbc.M112.442731. View

14.

Kwan T, Chadban S, Ma J, Bao S, Alexander S, Wu H . IL-17 deficiency attenuates allograft injury and prolongs survival in a murine model of fully MHC-mismatched renal allograft transplantation. Am J Transplant. 2015; 15(6):1555-67. DOI: 10.1111/ajt.13140. View

15.

Ni B, Chen Z, Shu L, Shao Y, Huang Y, Tamrat N . Nrf2 Pathway Ameliorates Bladder Dysfunction in Cyclophosphamide-Induced Cystitis via Suppression of Oxidative Stress. Oxid Med Cell Longev. 2021; 2021:4009308. PMC: 8279868. DOI: 10.1155/2021/4009308. View

16.

Segaliny A, Brion R, Mortier E, Maillasson M, Cherel M, Jacques Y . Syndecan-1 regulates the biological activities of interleukin-34. Biochim Biophys Acta. 2015; 1853(5):1010-21. DOI: 10.1016/j.bbamcr.2015.01.023. View

17.

Chandran S, Mannon R . T cell-mediated rejection in kidney transplant recipients: The end(point) is also the beginning. Am J Transplant. 2022; 22(3):683-684. DOI: 10.1111/ajt.16964. View

18.

Bezie S, Picarda E, Ossart J, Tesson L, Usal C, Renaudin K . IL-34 is a Treg-specific cytokine and mediates transplant tolerance. J Clin Invest. 2015; 125(10):3952-64. PMC: 4607123. DOI: 10.1172/JCI81227. View

19.

Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D . The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2017; 18(2):293-307. PMC: 5817248. DOI: 10.1111/ajt.14625. View

20.

Ren J, Li J, Feng Y, Shu B, Gui Y, Wei W . Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis. J Pathol. 2017; 242(4):488-499. DOI: 10.1002/path.4921. View