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Teriflunomide inhibits activation-induced CD25 expression on T cells and may affect Foxp3-expressing regulatory T cells.
Research in Veterinary Science ( IF 2.4 ) Pub Date : 2020-05-17 , DOI: 10.1016/j.rvsc.2020.05.011
Agnieszka Jasiecka-Mikołajczyk 1 , Piotr Socha 2
Affiliation  

Teriflunomide (TER) is an immunomodulatory agent. Although the first reports on the use of TER in dogs have already appeared, immune mechanisms underlying the immunomodulatory effect of TER do not seem to have been fully elucidated yet. There were two aspects of this study. First, further insight into the mode of action of TER was gained by investigating its effect on the expression of IL-2 receptor α-chain (CD25) and Forkhead box P3 (Foxp3) by CD4+ and CD8+ T cells and apoptosis of these cells. Second, in view in the earlier lack of data on the effect of TER on T cells in dogs, the results of this study filled in this gap. TER at a concentration which can be achieved in vivo prevented or reduced the activation-induced CD25 expression on CD4+ and CD8+ T cells, respectively. Taking into consideration the role of CD25 in T cell proliferation, this effect may constitute an additional mechanism responsible for the antiproliferative effect of the drug. Under stimulation conditions, TER induced Foxp3 expression in Foxp3-negative CD4+ and CD8+ T cells, while down-regulating it under unstimulated conditions. These results suggest that TER may generate iTreg cells, but this process requires cell activation. TER was not found to affect on the absolute count and apoptosis of CD4+ and CD8+ T cells. The results suggest that the impairment of CD25 expression during T cell activation and generation of iTreg cells may constitute additional mechanisms, besides the principal one, underlying the immunomodulatory effect of TER.



中文翻译:

特立氟胺抑制激活诱导的T细胞CD25表达,并可能影响表达Foxp3的调节性T细胞。

特氟米特(TER)是一种免疫调节剂。尽管已经出现了有关在犬中使用TER的第一个报道,但尚未完全阐明TER的免疫调节作用的免疫机制。这项研究有两个方面。首先,通过研究其对CD4 +和CD8 + T细胞对IL-2受体α链(CD25)和叉头盒P3(Foxp3)表达的影响以及它们的凋亡,进一步了解TER的作用方式。细胞。第二,鉴于先前缺乏有关TER对犬T细胞影响的数据,这项研究的结果填补了这一空白。可以达到体内浓度的TER可以预防或减少CD4 +和CD8上激活诱导的CD25表达+ T细胞。考虑到CD25在T细胞增殖中的作用,这种作用可能构成负责该药物抗增殖作用的其他机制。在刺激条件下,TER诱导Foxp3阴性CD4 +和CD8 + T细胞中Foxp3表达,而在未刺激条件下下调它。这些结果表明,TER可能产生iTreg细胞,但是这个过程需要细胞激活。未发现TER对CD4 +和CD8 +的绝对计数和凋亡有影响T细胞。结果表明,除了主要机制外,T细胞活化和iTreg细胞生成过程中CD25表达的损伤可能构成了其他机制,这是TER免疫调节作用的基础。

更新日期:2020-05-17
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