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Teriflunomide inhibits activation-induced CD25 expression on T cells and may affect Foxp3-expressing regulatory T cells.
Res Vet Sci. 2020 May 17; 132:17-27.RV

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn, Poland. Electronic address: agnieszka.jasiecka@uwm.edu.pl.Department of Animal Reproduction with Clinic, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 14, 10-719 Olsztyn, Poland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32474261

Citation

Jasiecka-Mikołajczyk, Agnieszka, and Piotr Socha. "Teriflunomide Inhibits Activation-induced CD25 Expression On T Cells and May Affect Foxp3-expressing Regulatory T Cells." Research in Veterinary Science, vol. 132, 2020, pp. 17-27.
Jasiecka-Mikołajczyk A, Socha P. Teriflunomide inhibits activation-induced CD25 expression on T cells and may affect Foxp3-expressing regulatory T cells. Res Vet Sci. 2020;132:17-27.
Jasiecka-Mikołajczyk, A., & Socha, P. (2020). Teriflunomide inhibits activation-induced CD25 expression on T cells and may affect Foxp3-expressing regulatory T cells. Research in Veterinary Science, 132, 17-27. https://doi.org/10.1016/j.rvsc.2020.05.011
Jasiecka-Mikołajczyk A, Socha P. Teriflunomide Inhibits Activation-induced CD25 Expression On T Cells and May Affect Foxp3-expressing Regulatory T Cells. Res Vet Sci. 2020 May 17;132:17-27. PubMed PMID: 32474261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Teriflunomide inhibits activation-induced CD25 expression on T cells and may affect Foxp3-expressing regulatory T cells. AU - Jasiecka-Mikołajczyk,Agnieszka, AU - Socha,Piotr, Y1 - 2020/05/17/ PY - 2020/02/24/received PY - 2020/05/15/revised PY - 2020/05/15/accepted PY - 2020/6/1/pubmed PY - 2020/6/1/medline PY - 2020/6/1/entrez KW - CD25 KW - CD4(+) cells KW - CD8(+) cells KW - Dog KW - Foxp3 KW - Teriflunomide SP - 17 EP - 27 JF - Research in veterinary science JO - Res. Vet. Sci. VL - 132 N2 - 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. SN - 1532-2661 UR - https://www.unboundmedicine.com/medline/citation/32474261/Teriflunomide_inhibits_activation-induced_CD25_expression_on_T_cells_and_may_affect_Foxp3-expressing_regulatory_T_cells L2 - https://linkinghub.elsevier.com/retrieve/pii/S0034-5288(20)30252-6 DB - PRIME DP - Unbound Medicine ER -
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