Oclacitinib depletes canine CD4+ and CD8+ T cells in vitro

Autor: Tomasz Maślanka, Jerzy Jan Jaroszewski, Agnieszka Jasiecka-Mikołajczyk
Rok vydání: 2018
Předmět:
Zdroj: Research in Veterinary Science. 121:124-129
ISSN: 0034-5288
DOI: 10.1016/j.rvsc.2018.10.014
Popis: Oclacitinib (OCL) is a novel immunosuppressive agent approved for dogs that controls itch and inflammation in allergic disease via the inhibition of the JAK/STAT pathway. This paper investigates the in vitro effect of OCL, a novel Janus kinase inhibitor, on selected canine regulatory (Treg) and effector (Teff) CD4+ and CD8+ T cells. Exposure of peripheral blood lymphocytes to OCL did not affect the transcription factor Foxp3 (Forkhead Box P3 protein) expression in CD25+CD4+ and CD25+CD8+ T cells. Moreover, OCL did not influence constitutive CD25 expression on these cells although it reduced the activation-induced CD25 expression on CD4+ T cells. Unexpectedly, the research demonstrated the cytoreductive and proapoptotic effects of OCL on the cells examined. Exposure to OCL caused a dramatic loss of both CD4+ and CD8+ T cells and this effect was observed in both Treg and Teff cell subsets. On the one hand, cytoreductive and proapoptotic effects of OCL toward CD4+ and CD8+ Teff cells, as well as the drug-induced inhibition of CD4+ T cell activation, may be considered as additional mechanisms involved in producing anti-inflammatory and anti-allergic properties of the drug. On the other hand, these effects also represent the immunosuppressive action in the sense of an unwanted effect because CD4+ and CD8+ Teff cells play a crucial role in the production of cellular immunity. Further studies are needed to determine whether the use of OCL actually creates the risk of such action.
Databáze: OpenAIRE
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