Analysis of IL-17A, IL-17F, and MiR-146a-5p Prior to Transplantation and Their Role in Kidney Transplant Recipients

Overview

Journal J Clin Med

Specialty General Medicine

Date 2024 May 25

PMID 38792460

Authors

Barbara Wysoczanska

Marta Dratwa

Artur Nieszporek

Wanda Niepieklo-Miniewska

Dorota Kaminska

Tomasz Ramus

Julia Rasala

Magdalena Krajewska

Katarzyna Bogunia-Kubik

Affiliations

Soon will be listed here.

Abstract

: The balance between regulatory and Th17 cells plays an important role in maintaining the immune tolerance after kidney transplantation (KTx) which is essential for transplantation success, defined as a long graft survival and an absence of organ rejection. The present study aimed to assess whether the pretransplant characteristics of IL-17A and IL-17F, their receptors, as well as miR-146a-5p, an miRNA associated with IL-17A/F regulation, can predict KTx outcomes. : A group of 108 pre-KTx dialysis patients and 125 healthy controls were investigated for single nucleotide substitutions within genes coding for , , their / receptors, and . Genotyping was performed using LightSNiP assays. In addition, IL17-A/F serum concentrations were determined using ELISA while miR-146a-5p expression was analyzed by RT-PCR. : The (rs763780) allele prevailed in KTx recipients as compared to healthy individuals (OR = 23.59, < 0.0001) and was associated with a higher IL-17F serum level ( = 0.0381) prior to transplantation. Higher miR-146a-5p expression before KTx was more frequently detected in recipients with an increased IL-17A serum concentration ( = 0.0177). Moreover, (rs2275913) homozygosity was found to be associated with an increased incidence of deaths before KTx (OR = 4.17, = 0.0307). T-cell or acute rejection episodes were more frequently observed among patients with the allele of (rs2910164) (OR = 5.38, = 0.0531). genetic variants ( < 0.05) seem to be associated with eGFR values. : These results imply that (rs763780) polymorphism is associated with the serum level of this cytokine and may be related to the risk of renal disease and transplant rejection together with (rs2910164), while the (rs2275913) genotype may affect patients' survival before KTx.

References

Wu J, Zhang F, Zhang J, Sun Z, Wang W . Advances of miRNAs in kidney graft injury. Transplant Rev (Orlando). 2020; 35(1):100591. DOI: 10.1016/j.trre.2020.100591. View

Mota A, Vilaca S, das Merces Jr F, de Barros Pinheiro M, Teixeira-Carvalho A, Silveira A . Cytokines signatures in short and long-term stable renal transplanted patients. Cytokine. 2013; 62(2):302-9. DOI: 10.1016/j.cyto.2013.03.001. View

Park H, Shin S, Park M, Kim Y, Ahn C, Ha J . Association of IL-17F gene polymorphisms with renal transplantation outcome. Transplant Proc. 2014; 46(1):121-3. DOI: 10.1016/j.transproceed.2013.05.015. View

Zhang R . Donor-Specific Antibodies in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2017; 13(1):182-192. PMC: 5753302. DOI: 10.2215/CJN.00700117. View

Coto E, Gomez J, Suarez B, Tranche S, Diaz-Corte C, Ortiz A . Association between the IL17RA rs4819554 polymorphism and reduced renal filtration rate in the Spanish RENASTUR cohort. Hum Immunol. 2015; 76(2-3):75-8. DOI: 10.1016/j.humimm.2015.01.027. View

Ma L, Zhang H, Hu K, Lv G, Fu Y, Ayana D . The imbalance between Tregs, Th17 cells and inflammatory cytokines among renal transplant recipients. BMC Immunol. 2015; 16:56. PMC: 4581081. DOI: 10.1186/s12865-015-0118-8. View

Khan Z, Suthanthiran M, Muthukumar T . MicroRNAs and Transplantation. Clin Lab Med. 2019; 39(1):125-143. PMC: 6369703. DOI: 10.1016/j.cll.2018.10.003. View

Yang B, Wei W, Shi Y, Huang Z, Cai B, Zhang J . Genetic Variation in miR-146a Is Not Associated with Susceptibility to IgA Nephropathy in Adults from a Chinese Han Population. PLoS One. 2015; 10(10):e0139554. PMC: 4591345. DOI: 10.1371/journal.pone.0139554. View

Ma W, Yao X, Peng Q, Chen D . The protective and pathogenic roles of IL-17 in viral infections: friend or foe?. Open Biol. 2019; 9(7):190109. PMC: 6685926. DOI: 10.1098/rsob.190109. View

10.

Amrouche L, Desbuissons G, Rabant M, Sauvaget V, Nguyen C, Benon A . MicroRNA-146a in Human and Experimental Ischemic AKI: CXCL8-Dependent Mechanism of Action. J Am Soc Nephrol. 2016; 28(2):479-493. PMC: 5280013. DOI: 10.1681/ASN.2016010045. View

11.

Huang D, He Y, Liu Y, He H, Gu Z, Liu Y . The immunomodulation role of Th17 and Treg in renal transplantation. Front Immunol. 2023; 14:1113560. PMC: 9928745. DOI: 10.3389/fimmu.2023.1113560. View

12.

Shao Y, Li J, Cai Y, Xie Y, Ma G, Li Y . The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population. Mediators Inflamm. 2014; 2014:916202. PMC: 3950573. DOI: 10.1155/2014/916202. View

13.

Guo H, Ma K, Hao W, Jiao Y, Li P, Chen J . mir15a/mir16-1 cluster and its novel targeting molecules negatively regulate cardiac hypertrophy. Clin Transl Med. 2020; 10(8):e242. PMC: 7737755. DOI: 10.1002/ctm2.242. View

14.

Hirsch H, Brennan D, Drachenberg C, Ginevri F, Gordon J, Limaye A . Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation. 2005; 79(10):1277-86. DOI: 10.1097/01.tp.0000156165.83160.09. View

15.

Gilyazova I, Asadullina D, Kagirova E, Sikka R, Mustafin A, Ivanova E . MiRNA-146a-A Key Player in Immunity and Diseases. Int J Mol Sci. 2023; 24(16). PMC: 10454149. DOI: 10.3390/ijms241612767. View

16.

Li N, Wang J, Yu W, Dong K, You F, Si B . MicroRNA‑146a inhibits the inflammatory responses induced by interleukin‑17A during the infection of Helicobacter pylori. Mol Med Rep. 2018; 19(2):1388-1395. DOI: 10.3892/mmr.2018.9725. View

17.

Krajewska M, Koscielska-Kasprzak K, Kaminska D, Zabinska M, Myszka-Kozlowska M, Gomulkiewicz A . Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation. J Immunol Res. 2019; 2019:7452019. PMC: 6341262. DOI: 10.1155/2019/7452019. View

18.

Guerra G, Srinivas T, Meier-Kriesche H . Calcineurin inhibitor-free immunosuppression in kidney transplantation. Transpl Int. 2007; 20(10):813-27. DOI: 10.1111/j.1432-2277.2007.00528.x. View

19.

Witowski J, Kamhieh-Milz J, Kawka E, Catar R, Jorres A . IL-17 in Peritoneal Dialysis-Associated Inflammation and Angiogenesis: Conclusions and Perspectives. Front Physiol. 2018; 9:1694. PMC: 6275317. DOI: 10.3389/fphys.2018.01694. View

20.

Lofgren S, Frostegard J, Truedsson L, Pons-Estel B, DAlfonso S, Witte T . Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene. Genes Immun. 2012; 13(3):268-74. PMC: 3640319. DOI: 10.1038/gene.2011.84. View