期刊
RESEARCH IN VETERINARY SCIENCE
卷 121, 期 -, 页码 124-129出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.rvsc.2018.10.014
关键词
Oclacitinib; CD4(+) cells; CD8(+) cells; CD25; Treg; Dog
资金
- University of Warmia and Mazury in Olsztyn [15.610.008-300]
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.
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