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

Agnieszka Jasiecka-Mikołajczyk1, Jerzy J Jaroszewski1, Tomasz Maślanka1

  • 1Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowski Street 13, 10-719 Olsztyn, Poland.

Research in Veterinary Science
|November 5, 2018
PubMed

Insights

Oclacitinib (OCL), a JAK inhibitor, unexpectedly reduced canine T cells (CD4+ and CD8+), including regulatory and effector subsets. While potentially contributing to anti-inflammatory effects, this immunosuppression warrants further investigation for safety concerns.

Area of Science:

  • Immunology
  • Veterinary Pharmacology
  • Cell Biology

Background:

  • Oclacitinib (OCL) is an immunosuppressive drug used in dogs to manage allergic skin disease by inhibiting the JAK/STAT pathway.
  • Understanding OCL's precise effects on canine T cell subsets is crucial for evaluating its therapeutic efficacy and potential side effects.

Purpose of the Study:

  • To investigate the in vitro effects of OCL on canine regulatory T cells (Tregs) and effector T cells (Teffs), specifically CD4+ and CD8+ T cell subsets.
  • To assess OCL's impact on T cell activation markers and its potential cytoreductive and proapoptotic effects.

Main Methods:

  • Peripheral blood lymphocytes from dogs were exposed to OCL in vitro.
  • Flow cytometry was used to analyze the expression of Foxp3 and CD25 on CD4+ and CD8+ T cells.
  • Cytoreductive and proapoptotic effects of OCL on T cell populations were evaluated.

Main Results:

  • OCL did not alter Foxp3 expression in CD25+CD4+ and CD25+CD8+ T cells.
  • OCL did not affect constitutive CD25 expression but reduced activation-induced CD25 expression on CD4+ T cells.
  • Unexpectedly, OCL exhibited significant cytoreductive and proapoptotic effects, leading to a dramatic loss of both CD4+ and CD8+ T cells across Treg and Teff subsets.

Conclusions:

  • OCL's reduction of T cell activation and its cytoreductive/proapoptotic effects on T cells may contribute to its anti-inflammatory and anti-allergic properties.
  • These observed immunosuppressive effects, however, raise concerns about potential adverse outcomes due to the critical role of T cells in cellular immunity.
  • Further research is necessary to determine the clinical implications and risks associated with OCL-induced T cell depletion in dogs.
Keywords:
CD25CD4(+) cellsCD8(+) cellsDogOclacitinibTreg

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