Exogenous IL-10 induces corneal transplantation immune tolerance by a mechanism associated with the altered Th1/Th2 cytokine ratio and the increased expression of TGF-β

Li,Bing; Tian,Lihua; Diao,Yumei; Li,Xue; Zhao,Liying; Wang,Xuefeng

doi:10.3892/mmr.2014.2073

Exogenous IL-10 induces corneal transplantation immune tolerance by a mechanism associated with the altered Th1/Th2 cytokine ratio and the increased expression of TGF-β

Authors:
- Bing Li
- Lihua Tian
- Yumei Diao
- Xue Li
- Liying Zhao
- Xuefeng Wang
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Affiliations: Department of Ophthalmology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China, Department of Otolaryngology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China
Published online on: March 27, 2014 https://doi.org/10.3892/mmr.2014.2073
Pages: 2245-2250

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Abstract

The aim of the present study was to examine the effect of exogenous IL-10 transfected rat dendritic cells (DCs) in corneal allografts. Rat lymphocyte separation medium and a cytokine induction method was used to extract and culture precursor cells of rat bone marrow-derived dendritic cells. A corneal transplant model was established, with Sprague‑Dawley (SD) rats as the recipients and Wistar rats as the donors. Flow cytometry (FCM) was used to detect the expression of CD83, which indicates a mature dendritic cell, and a specific cell surface stimulatory molecule CD86. Western blot analysis was used to detect interleukin (IL)-10 protein expression and RT-PCR was used to detect cytokine IL-10, IL-2 and TGF-β mRNA expression in each group. Compared with the other groups, the survival time of corneal grafts in the IL-10-green fluorescent protein (GFP)-DC group was significantly prolonged and H&E staining demonstrated mild graft edema and inflammatory cell infiltration. There was a high expression of IL-10 and a low expression of the surface antigens, CD83 and CD86, with a lower proliferation of T lymphocytes in the IL-10-GFP-DC group. The expression of IL-10 and TGF-β in the IL-10‑GFP-DC group was higher than that in the other groups, while the expression of IL-2 was lower. The transfection of the IL-10 gene inhibited dendritic cell maturation. IL-10 gene‑modified immature dendritic cells (imDC) were able to inhibit corneal allograft rejection and induce immune tolerance to prolong the survival time of the corneal graft. The Th1/Th2 deviation and the high expression of TGF-β may lead to immune tolerance.

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1	Oliva MS, Schottman T and Gulati M: Turning the tide of corneal blindness. Indian J Ophthalmol. 60:423–427. 2012. View Article : Google Scholar : PubMed/NCBI
2	Tan DT, Dart JK, Holland EJ and Kinoshita S: Corneal transplantation. Lancet. 379:1749–1761. 2012. View Article : Google Scholar : PubMed/NCBI
3	Perera C, Jhanji V, Lamoureux E, Pollock G, Favilla I and Vajpayee RB: Clinical presentation, risk factors and treatment outcomes of first allograft rejection after penetrating keratoplasty in early and late postoperative period. Eye (Lond). 26:711–717. 2012. View Article : Google Scholar
4	Song J and Huang YF: Characteristics of corneal endothelium during allograft rejection after corneal transplantation. Zhonghua Yan Ke Za Zhi. 47:281–284. 2011.(In Chinese).
5	Lowe MT, Keane MC, Coster DJ and Williams KA: The outcome of corneal transplantation in infants, children, and adolescents. Ophthalmology. 118:492–427. 2011. View Article : Google Scholar : PubMed/NCBI
6	Chen X, Zhao S, Tang X, Ge H and Liu P: Neutralization of mouse interleukin-17 bioactivity inhibits corneal allograft rejection. Mol Vis. 17:2148–2156. 2011.PubMed/NCBI
7	Hegde S and Niederkorn JY: The role of cytotoxic T lymphocytes in corneal allograft rejection. Invest Ophthalmol Vis Sci. 41:3341–3347. 2000.PubMed/NCBI
8	Shi WY and Xie LX: The corneal allograft rejection features in CD4 and CD8 knock-out mice. Zhonghua Yan Ke Za Zhi. 41:350–354. 2005.(In Chinese).
9	Jessup CF, Brereton HM, Sykes PJ, Thiel MA, Coster DJ and Williams KA: Local gene transfer to modulate rat corneal allograft rejection. Invest Ophthalmol Vis Sci. 46:1675–1681. 2005. View Article : Google Scholar : PubMed/NCBI
10	Wang DJ, Guo HL, Huang YF, Chen GJ, Zhang H and Li Y: Effects of a new immunodepressant J2 on lymphocytic secretion of interleukin 10 and interferon gamma in mice after corneal allograft. Journal of Clinical Rehabilitative Tissue Engineering Research. 31:5797–5800. 2011.
11	Masli S, Turpie B, Hecker KH and Streilein JW: Expression of thrombospondin in TGFβ-treated APCs and its relevance to their immune deviation-promoting properties. J Immunol. 168:2264–2273. 2002.
12	Okamoto S, Hara Y and Streilein JW: Induction of anterior chamber-associated immune deviation with lymphoreticular allogeneic cells. Transplantation. 59:377–381. 1995.PubMed/NCBI
13	Sano Y, Okamoto S and Streilein JW: Induction of donor-specific ACAID can prolong orthotopic corneal allograft survival in “high-risk” eyes. Curr Eye Res. 16:1171–1174. 1997.PubMed/NCBI
14	Tiao MM, Lu L, Huang LT, et al: Cross-tolerance of recipient-derived transforming growth factor-beta dendritic cells. Transplant Proc. 39:281–282. 2007. View Article : Google Scholar : PubMed/NCBI
15	Yan F, Cai L, Hui YN, Wang YS and Meng H: Suppression effects of TGFβ2 -DC on corneal allograft rejection. Guoji Yanke Zazhi. 2:346–349. 2007.(In Chinese).
16	Ezzelarab M and Thomson AW: Tolerogenic dendritic cells and their role in transplantation. Semin Immunol. 23:252–263. 2011. View Article : Google Scholar : PubMed/NCBI
17	Wang T, Xu L, Li H, et al: Immature CD4⁺ dendritic cells conditioned with donor kidney antigen prolong renal allograft survival in rats. Chin Med J (Engl). 125:2530–2537. 2012.
18	Liu WH, Liu JJ, Wu J, et al: Novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem cells via interleukin-10 and the JAK1/STAT3 signaling pathway. PLoS One. 8:e554872013. View Article : Google Scholar : PubMed/NCBI
19	Li B and Hong J: Effects of topically administered rapamycin on cytokine expression after penetrating keratoplasty in rats. Chinese Ophthalmic Research. 25:850–853. 2007.
20	van Kooten C, Lombardi G, Gelderman KA, et al: Dendritic cells as a tool to induce transplantation tolerance: obstacles and opportunities. Transplantation. 91:2–7. 2011.PubMed/NCBI
21	Han B and Hu YH: Inhibitory mechanism of CTLA4Ig-transfected DC in corneal transplantation. Chinese Ophthalmic Research. 25:347–350. 2007.
22	Ouyang J, Fan C, Wen D, et al: Donor antigen-loaded IKK2dn gene-modified dendritic cells prolong allograft survival. Scand J Immunol. 71:336–344. 2010. View Article : Google Scholar : PubMed/NCBI
23	Qu XY, Wang Y and Qin CH: Effects of U0126 on the process of immature dendritic cells inducing naive CD4⁺ T cells to differentiate to Treg cells in vitro. The Journal of Practical Medicine. 26:4476–4479. 2010.
24	Yang S, Li W, Liu W, et al: IL-10 gene modified dendritic cells induced antigen-specific tolerance in experimental autoimmune myocarditis. Clin Immunol. 121:63–73. 2006. View Article : Google Scholar : PubMed/NCBI
25	Kushwah R, Oliver JR, Duan R, Zhang L, Keshavjee S and Hu J: Induction of immunological tolerance to adenoviral vectors by using a novel dendritic cell-based strategy. J Virol. 86:3422–3435. 2012. View Article : Google Scholar : PubMed/NCBI
26	Penna G and Adorini L: 1 Alpha,25-dihydroxyvitamin D₃ inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol. 164:2405–2411. 2000.PubMed/NCBI