Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation

Li Xianliang; Bai Chun; Yang Long; Li Han; Lyu Shaocheng; Zhu Jiqiao; Ma Jun; Kou Jiantao; He Qiang

doi:10.3969/j.issn.1674-7445.2019.04.011

Volume 10 Issue 4

Jul. 2019

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Li Xianliang, Bai Chun, Yang Long, et al. Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation[J]. ORGAN TRANSPLANTATION, 2019, 10(4): 416-422. doi: 10.3969/j.issn.1674-7445.2019.04.011

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Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation

doi: 10.3969/j.issn.1674-7445.2019.04.011

Department of Hepatobiliary, Pancreatic and Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

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Corresponding author: Li Xianliang, Email: lixianliangbjcy@126.com
Received Date: 2019-04-25
Available Online: 2021-01-19
Publish Date: 2019-07-15

Abstract

Abstract

Objective To investigate the relationship between immune tolerance and the changes of helper T cell (Th), regulatory T cell (Treg) cytokines, related signaling pathway proteins during immune tolerance process in rat models of liver transplantation. Methods The orthotopic liver transplantation rat models were established by double-cuff technique. All rats were divided into 3 groups. In the operative control group (n=6), sham operation was performed without liver transplantation. In the short-term group (n=10), the rats survived for 10 d after liver transplantation. In the immune tolerance group (n=10), the rats survived for 100 d after operation and the function of the transplanted liver was restored to normal. The expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Th1 cytokines [interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α], Th2 cytokines (IL-4, IL-5, IL-6 and IL-13), Th17 cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A], Treg cytokines [IL-10, transforming growth factor (TGF)-β and IL-12p] were quantitatively measured. The serum sample of rats in each group was detected by protein chip analysis. Results Compared with the operative control group, the AST level in the short-term group was significantly down-regulated, whereas the ALT level was significantly up-regulated (both P < 0.05). However, the AST and ALT levels did not significantly differ between the immune tolerance group and operative control group (both P > 0.05). In the liver tissues of rats in each group, the expression levels of Th1 cytokines IFN-γ and IL-2 in the short-term group were significantly higher than those in the operative control group (both P < 0.05). The expression level of Th2 cytokine IL-4 in the immune tolerance group was significantly lower than that in the operative control group (P < 0.05). The expression levels of Th2 cytokines IL-5, IL-6 and IL-13 in the short-term group were significantly lower than those in the operative control group (all P < 0.05). The expression level of IL-17A in the immune tolerance group was significantly higher than that in the operative control group (P < 0.05). In the immune tolerance group, the expression levels of IL-10and IL-12p were significantly higher than those in the operative control group (both P < 0.05). The expression level of TGF-β in the short-term group was significantly higher than that in the operative control group (P < 0.05). Compared with the operative control group, the expression levels of intercellular adhesion molecule (ICAM)-1, pro-platelet basic protein (Ppbp), Neuropilin-2, Notch-2 protein in the short-term group were significantly up-regulated (all P < 0.05). The expression levels of CXC chemokine ligand 17 (CXCL17), ICAM-1 and Neuroleptin-2 protein were markedly up-regulated (all P < 0.05), whereas that of B7-1 protein was significantly down-regulated (P < 0.05) in the immune tolerance group. Conclusions Treg cytokines (IL-10, TGF-β and IL-12p), IL-6, IL-17 and trans-membrane signaling pathway molecules (ICAM-1, Neuropilin-2, B7-1 proteins) play a pivotal role in the natural immune tolerance process of rat models of liver transplantation.
- Liver transplantation,
- Immune tolerance,
- Helper T cell,
- Regulatory T cell,
- Signaling pathway protein

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References

[1]	李坤, 孔伟浩, 张俊斌, 等.MiR-155在大鼠肝移植术后排斥反应中作用机制的研究[J].器官移植, 2018, 9(3):194-199.DOI: 10.3969/j.issn.1674-7445.2018.03.005. LI K, KONG WH, ZHANG JB, et al. Study of miR-155 in the mechanism of rejection after liver transplantation in rats[J]. Organ Transplant, 2018, 9(3):194-199. DOI: 10.3969/j.issn.1674-7445.2018.03.005.
[2]	叶林森, 张英才, 唐晖, 等.长期生存的肝移植受者外周血免疫细胞分析[J].中华普通外科杂志, 2017, 32(6):508-511.DOI: 10.3760/cma.j.issn.1007-631X.2017.06.014. YE LS, ZHANG YC, TANG H, et al. Peripheral blood immune cells in long-term survival patients after liver transplantation[J]. Chin J Gen Surg, 2017, 32(6):508-511. DOI: 10.3760/cma.j.issn.1007-631X.2017.06.014.
[3]	HWANG W, LEE J. Pathophysiologic implications of cytokines secretion during liver transplantation surgery[J]. Int J Med Sci, 2018, 15(14):1737-1745. DOI: 10.7150/ijms.28382.
[4]	LÓPEZ-ABENTE J, BERNALDO-DE-QUIRÓS E, CAMINO M, et al. Immune dysregulation and Th2 polarization are associated with atopic dermatitis in heart-transplant children: a delicate balance between risk of rejection or atopic symptoms[J]. Am J Transplant, 2019, 19(5):1536-1544. DOI: 10.1111/ajt.15245.
[5]	ETEGHADI A, PAK F, AHMADPOOR P, et al. Th1, Th2, Th17 cell subsets in two different immunosuppressive protocols in renal allograft recipients (sirolimus vs mycophenolate mofetil): a cohort study[J]. Int Immunopharmacol, 2019, 67:319-325. DOI: 10.1016/j.intimp.2018.12.033.
[6]	LIU M, LI S, LI MO. TGF-β control of adaptive immune tolerance: a break from Treg cells[J]. Bioessays, 2018, 40(11):e1800063. DOI: 10.1002/bies.201800063.
[7]	HOE E, ANDERSON J, NATHANIELSZ J, et al. The contrasting roles of Th17 immunity in human health and disease[J]. Microbiol Immunol, 2017, 61(2):49-56. DOI: 10.1111/1348-0421.12471.
[8]	NOACK M, MIOSSEC P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases[J]. Autoimmun Rev, 2014, 13(6):668-677. DOI: 10.1016/j.autrev.2013.12.004.
[9]	ZHENG L, LI Z, LING W, et al. Exosomes derived from dendritic cells attenuate liver injury by modulating the balance of Treg and Th17 cells after ischemia reperfusion[J]. Cell Physiol Biochem, 2018, 46(2):740-756. DOI: 10.1159/000488733.
[10]	ZHANG A, WANG K, ZHOU C, et al. Knockout of microRNA-155 ameliorates the Th1/Th17 immune response and tissue injury in chronic rejection[J]. J Heart Lung Transplant, 2017, 36(2):175-184. DOI: 10.1016/j.healun.2016.04.018.
[11]	LU L, LI G, RAO J, et al. In vitro induced CD4(+)CD25(+)Foxp3(+) Tregs attenuate hepatic ischemia-reperfusion injury[J]. Int Immunopharmacol, 2009, 9(5):549-552. DOI: 10.1016/j.intimp.2009.01.020.
[12]	PERUCHA E, MELCHIOTTI R, BIBBY JA, et al. The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells[J]. Nat Commun, 2019, 10(1):498. DOI: 10.1038/s41467-019-08332-9.
[13]	PILAT N, MAHR B, GATTRINGER M, et al. CTLA4Ig improves murine iTreg induction via TGFβ and suppressor function in vitro[J]. J Immunol Res, 2018:2484825. DOI: 10.1155/2018/2484825.
[14]	TEIJEIRA A, HUNTER MC, RUSSO E, et al. T cell migration from inflamed skin to draining lymph nodes requires intralymphatic crawling supported by ICAM-1/LFA-1 interactions[J]. Cell Rep, 2017, 18(4):857-865. DOI: 10.1016/j.celrep.2016.12.078.
[15]	SILVA PDE M, BIER J, PAIATTO LN, et al. Tolerogenic dendritic cells on transplantation: immunotherapy based on second signal blockage[J]. J Immunol Res, 2015:856707. DOI: 10.1155/2015/856707.
[16]	SCHELLENBURG S, SCHULZ A, POITZ DM, et al. Role of neuropilin-2 in the immune system[J]. Mol Immunol, 2017, 90:239-244. DOI: 10.1016/j.molimm.2017.08.010.
[17]	BURGHARDT S, CLAASS B, ERHARDT A, et al. Hepatocytes induce Foxp3⁺ regulatory T cells by notch signaling[J]. J Leukoc Biol, 2014, 96(4):571-577. DOI: 10.1189/jlb.2AB0613-342RR.
[18]	FINSTERBUSCH M, NORMAN MU, HALL P, et al. Platelet retention in inflamed glomeruli occurs via selective prolongation of interactions with immune cells[J]. Kidney Int, 2019, 95(2):363-374. DOI: 10.1016/j.kint.2018.08.042.
[19]	REN J, ZHOU T, PILLI VSS, et al. Novel paracrine functions of smooth muscle cells in supporting endothelial regeneration following arterial injury[J]. Circ Res, 2019, 124(8):1253-1265. DOI: 10.1161/CIRCRESAHA.118.314567.
[20]	SHARPE AH, FREEMAN GJ. The B7-CD28 superfamily[J]. Nat Rev Immunol, 2002, 2(2):116-126. doi: 10.1038/nri727
[21]	SHEN H, WU N, NANAYAKKARA G, et al. Co-signaling receptors regulate T-cell plasticity and immune tolerance[J]. Front Biosci (Landmark Ed), 2019, 24:96-132. doi: 10.2741/4710
[22]	LI K, CHENG X, TILEVIK A, et al. In situ and in silico kinetic analyses of programmed cell death-1 (PD-1) receptor, programmed cell death ligands, and B7-1 protein interaction network[J]. J Biol Chem, 2017, 292(16):6799-6809. DOI: 10.1074/jbc.M116.763888.
[23]	WATANABE M, FUJIHARA C, RADTKE AJ, et al. Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells[J]. J Exp Med, 2017, 214(9):2795-2810. DOI: 10.1084/jem.20161955.
[24]	KANG S, ZHANG C, OHNO T, et al. Unique B7-H1 expression on masticatory mucosae in the oral cavity and trans-coinhibition by B7-H1-expressing keratinocytes regulating CD4⁺ T cell-mediated mucosal tissue inflammation[J]. Mucosal Immunol, 2017, 10(3):650-660. DOI: 10.1038/mi.2016.89.

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Changes of Th, Treg cytokines and signaling pathway proteins during immune tolerance process in rat models of liver transplantation

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