Suppressive effects of vitamin C-treated induced-regulatory T cells on heart allograft rejection under vitamin C-deficient or -sufficient conditions.

Suppressive effects of vitamin C-treated induced-regulatory T cells on heart allograft rejection under vitamin C-deficient or -sufficient conditions.
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DOI:
10.1371/journal.pone.0246967
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Yang J
Yang J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hwang JH;Piao H;Jang JY;Lee SK;Han D;Lee GM;Go C;Kim Y;Oh KI;Kang JS;Yan JJ;Yang J

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维生素C处理的诱导调节性T细胞(V-iTcells)的Foxp 3稳定性上级常规iTcells(C-iTcells)。然而,在维生素C缺乏的条件下,如在人类中所见,V-iTdR在同种异体移植排斥反应中的作用仍不清楚。我们的目的是阐明维生素C治疗对gulo基因敲除(Gulo-KO)小鼠以及野生型(WT)小鼠iTclad的产生和维持的作用,以及V-iTclad对Gulo-KO或WT受体小鼠中心脏同种异体移植物排斥的体外和体内抑制作用。在WT和Gulo-KO小鼠中,C-和V-iTdR之间iTdR的转化效率相似。来自WT或Gulo-KO小鼠的V-iTdR显示出比C-iTdR更好的体外Foxp 3稳定性,尽管WT V-iTdR和Gulo-KO V-iTdR之间没有差异。此外,来自WT或Gulo-KO小鼠的V-iTdR比C-iTdR更好地抑制体外T细胞增殖。在过继转移C-或V-iTlR后,进行从BALB/c小鼠到WT或维生素C缺乏的Gulo-KO C57 BL/6 J小鼠的异养心脏移植。在WT和Gulo-KO小鼠中,V-iTdR和C-iTdR延长了心脏同种异体移植物的存活。然而,C-和V-iTreg组之间没有差异。补充低剂量或高剂量的维生素C并没有引起接受V-iTdR的Gulo-KO受体心脏移植物存活率的显著变化。总之,在WT或维生素C缺乏的受体中,V-iTdR对心脏移植物存活的抑制作用并不比C-iTdR好。
Foxp3 stability of vitamin C-treated induced-regulatory T cells (V-iTregs) is superior to that of conventional iTregs (C-iTregs). However, the role of V-iTregs in allograft rejection under vitamin C-deficient conditions, such as those seen in humans, remains unclear. We aimed to elucidate the role of vitamin C treatment on generation and maintenance of iTregs from gulo knockout (Gulo-KO) mice as well as wild type (WT) mice, and in vitro and in vivo suppressive effects of V-iTregs on heart allograft rejection in either Gulo-KO or WT recipient mice. Conversion efficiency of iTregs was similar between C- and V-iTregs in both WT and Gulo-KO mice. V-iTregs from WT or Gulo-KO mice showed better in vitro Foxp3 stability than C-iTregs, although there was no difference between WT V-iTregs and Gulo-KO V-iTregs. Furthermore, V-iTregs from WT or Gulo-KO mice suppressed in vitro T cell proliferation better than C-iTregs. Heterotrophic heart transplantation from BALB/c mice to WT or vitamin C-deficient Gulo-KO C57BL/6J mice was performed following adoptive transfer of C- or V-iTregs. V-iTregs as well as C-iTregs prolonged heart allograft survival in WT and Gulo-KO mice. However, there was no difference between the C- and V-iTreg groups. Supplementation of low- or high-dose vitamin C did not induce significant changes in heart allograft survival in Gulo-KO recipients that had received V-iTregs. In conclusion, V-iTregs do not exert better suppressive effects on heart allograft survival than C-iTregs in either WT or vitamin C-deficient recipients.
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