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All-trans retinoid acid promotes allogeneic corneal graft survival in mice by regulating Treg-Th17 balance in the presence of TGF-β.
BMC Immunol 2015; 16:17BI

Abstract

BACKGROUND

All-trans retinoid acid (ATRA) has been proven to skew Regulatory T cell-T helper 17 cell (Treg-Th17) balance toward Treg in vitro, favoring graft acceptance. However, its in vivo effect after solid organ transplantation is under investigation.

RESULTS

BALB/c mice were given orthotopic corneal grafts from C57BL/6 donors, and recipient mice were administered with ATRA, TGF-β, and the combination of both agents for 8 weeks after surgery. We found that a mixed treatment of ATRA and TGF-β significantly promoted graft survival. Moreover, with the presence of TGF-β, ATRA upregulated CD4(+)CD25(+)Foxp3(+)Treg cells and suppressed Th17 cells in the blood, spleen and draining lymph nodes of recipient mice, as well as enhanced the Foxp3 expression and inhibited the RORγt expression in grafts and peripheral blood mononuclear cells (PBMCs). Simultaneously, increased number of Foxp3+ cells and decreased number of IL-17+ cells in conjunctiva were found in recipients with mixed treatment, along with reduced IL-17 level in serum and aqueous humor and increased IL-10 level in aqueous humor. Tregs isolated from recipient mice treated with ATRA + TGF-β presented the strongest suppressive activity in vitro.

CONCLUSIONS

Combined application of ATRA and TGF-β may shift the Th17-Treg balance toward Tregs, hence facilitating the induction of immunological tolerance after allogenic corneal transplantation and representing a potential therapeutic approach in the treatment of posttransplant rejection.

Authors+Show Affiliations

Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. miaciswang@gmail.com.Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. wangwentao_ann@163.com. Research Center, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. wangwentao_ann@163.com.Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. jianjiang-xu@163.com.Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. stevenboy88@msn.com.Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. angela_le1977@163.com. Research Center, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. angela_le1977@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25887926

Citation

Wang, Xin, et al. "All-trans Retinoid Acid Promotes Allogeneic Corneal Graft Survival in Mice By Regulating Treg-Th17 Balance in the Presence of TGF-β." BMC Immunology, vol. 16, 2015, p. 17.
Wang X, Wang W, Xu J, et al. All-trans retinoid acid promotes allogeneic corneal graft survival in mice by regulating Treg-Th17 balance in the presence of TGF-β. BMC Immunol. 2015;16:17.
Wang, X., Wang, W., Xu, J., Wu, S., & Le, Q. (2015). All-trans retinoid acid promotes allogeneic corneal graft survival in mice by regulating Treg-Th17 balance in the presence of TGF-β. BMC Immunology, 16, p. 17. doi:10.1186/s12865-015-0082-3.
Wang X, et al. All-trans Retinoid Acid Promotes Allogeneic Corneal Graft Survival in Mice By Regulating Treg-Th17 Balance in the Presence of TGF-β. BMC Immunol. 2015 Mar 19;16:17. PubMed PMID: 25887926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - All-trans retinoid acid promotes allogeneic corneal graft survival in mice by regulating Treg-Th17 balance in the presence of TGF-β. AU - Wang,Xin, AU - Wang,Wentao, AU - Xu,Jianjiang, AU - Wu,Suqian, AU - Le,Qihua, Y1 - 2015/03/19/ PY - 2014/01/24/received PY - 2015/03/09/accepted PY - 2015/4/19/entrez PY - 2015/4/19/pubmed PY - 2016/1/16/medline SP - 17 EP - 17 JF - BMC immunology JO - BMC Immunol. VL - 16 N2 - BACKGROUND: All-trans retinoid acid (ATRA) has been proven to skew Regulatory T cell-T helper 17 cell (Treg-Th17) balance toward Treg in vitro, favoring graft acceptance. However, its in vivo effect after solid organ transplantation is under investigation. RESULTS: BALB/c mice were given orthotopic corneal grafts from C57BL/6 donors, and recipient mice were administered with ATRA, TGF-β, and the combination of both agents for 8 weeks after surgery. We found that a mixed treatment of ATRA and TGF-β significantly promoted graft survival. Moreover, with the presence of TGF-β, ATRA upregulated CD4(+)CD25(+)Foxp3(+)Treg cells and suppressed Th17 cells in the blood, spleen and draining lymph nodes of recipient mice, as well as enhanced the Foxp3 expression and inhibited the RORγt expression in grafts and peripheral blood mononuclear cells (PBMCs). Simultaneously, increased number of Foxp3+ cells and decreased number of IL-17+ cells in conjunctiva were found in recipients with mixed treatment, along with reduced IL-17 level in serum and aqueous humor and increased IL-10 level in aqueous humor. Tregs isolated from recipient mice treated with ATRA + TGF-β presented the strongest suppressive activity in vitro. CONCLUSIONS: Combined application of ATRA and TGF-β may shift the Th17-Treg balance toward Tregs, hence facilitating the induction of immunological tolerance after allogenic corneal transplantation and representing a potential therapeutic approach in the treatment of posttransplant rejection. SN - 1471-2172 UR - https://www.unboundmedicine.com/medline/citation/25887926/All_trans_retinoid_acid_promotes_allogeneic_corneal_graft_survival_in_mice_by_regulating_Treg_Th17_balance_in_the_presence_of_TGF_β_ L2 - https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-015-0082-3 DB - PRIME DP - Unbound Medicine ER -