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

• Published in: Research in veterinary science 2018-12, Vol.121, p.124-129
• Main Authors: Jasiecka-Mikołajczyk, Agnieszka, Jaroszewski, Jerzy J., Maślanka, Tomasz
• Format: Article
• Language: English
• Subjects: Allergies; Animals; Apoptosis; CD25; CD25 antigen; CD4 antigen; CD4+ cells; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8+ cells; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell-mediated immunity; Cellular manufacture; Cytokines; Dermatitis; Disease; Disease control; Dog; Dogs; Enzyme inhibitors; Exposure; Forkhead protein; Foxp3 protein; Hypotheses; Immunity; Immunosuppression; Immunosuppressive Agents - pharmacology; Inflammation; Inhibition; Janus kinase; Janus Kinase 1 - antagonists & inhibitors; Kinases; Lymphocytes; Lymphocytes T; Oclacitinib; Pathogenesis; Peripheral blood; Proteins; Pruritus; Pyrimidines - pharmacology; Signal transduction; Studies; Sulfonamides - pharmacology; Treg; Veterinary medicine
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2018.10.014

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. •Oclacitinib reduces the absolute count of canine CD4+ and CD8+ T cells.•Oclacitinib does not affect Foxp3 expression in canine CD4+ and CD8+ T cells.•Oclacitinib reduces the activation-induced CD25 expression on canine CD4+ T cells.•Oclacitinib may exert the proapoptotic action on canine CD4+ and CD8+ T cells.