Treatment with oclacitinib, a Janus kinase inhibitor, down-regulates and up-regulates CD25 and Foxp3 expression, respectively, in peripheral blood T cells of dogs with atopic dermatitis.

Abstract

Background: Oclacitinib (OCL), a Janus kinase inhibitor, is a novel immunomodulatory/immunosuppressive agent which is an approved as the first-line treatment for atopic dermatitis (AD) in dogs. The aim of the study was to investigate the effects of OCL on CD4⁺ and CD8⁺ T cells and their selected subsets under clinical conditions, i.e. in dogs suffering from AD, in terms of both safety and immune mechanisms underlying its therapeutic actions. Eight dogs were treated for 28 days with OCL at the recommended dose. Blood samples were taken at day 0, 7, 14 and 28.

Results: The study showed that the mean percentage and absolute count of CD4⁺ and CD8⁺ T cells on the 14th and 28th day of the treatment with OCL did not differ from the corresponding baseline values, i.e. those before the treatment. On the 7th day of the treatment, the mean absolute count of CD4⁺ T cells and the mean percentage and absolute count of CD8⁺ T cells were significantly increased. The research found that on the 14th day of the treatment, the mean percentage and absolute count of CD25⁺CD4⁺ and CD25⁺CD8⁺ T cells were significantly decreased; the reduction in the percentage of CD25⁺CD4⁺ T cells persisted on 28th day of the treatment. A two-week treatment with OCL resulted in an increase in the mean percentage of Foxp3⁺CD4⁺ T cells, and this effect was sustained at the last time point. The treatment with OCL decreased the eosinophil level but does not affect the absolute counts of basophils, monocytes and neutrophils.

Conclusions: The findings of the study strongly suggest that: (a) in terms of the impact of OCL on the number of PB CD4⁺ and CD8⁺ T cells, monthly treatment with the drug should be considered as a relatively safe; (b) the eosinophil-reducing effect and the down-regulation of the AD up-regulated CD25 expression on CD4⁺ Teff cells may constitute significant elements of the mechanism of action underlying the therapeutic effects of the drug in the treatment of canine AD; (c) the generation of inducible Foxp3-expressing CD4⁺ regulatory T cells - resulting in the shift of the CD4⁺ Treg cell (i.e. Foxp3⁺CD4⁺)/activated Teff (i.e. CD25⁺CD4⁺) cell balance toward an increased proportion of Treg cells - may be considered as additional mechanism involved in producing the immunomodulatory/immunosuppressive properties of OCL.