The Inhibition of Glycolysis in T Cells by a Jak Inhibitor Ameliorates the Pathogenesis of Allergic Contact Dermatitis in Mice

Abstract

Allergic contact dermatitis (ACD) and atopic dermatitis (AD) develop through delayed-type hypersensitivity reactions mediated by T cells. The development of immunomodulatory drugs, such as Jak inhibitors (jakinibs), would be useful for the long-term management of these diseases due to their profile of favorable adverse effects. However, the efficacy of jakinibs for ACD treatment has not been fully determined under a variety of settings. Therefore, we evaluated the effects of ruxolitinib (Rux), a jakinib for Jak1 and Jak2, using a mouse ACD model. As a result, the lower numbers of immune cells including CD4+ T cells, CD8+ T cells, neutrophils and possibly macrophages as well as milder pathophysiological aspects have been observed in the inflamed skin of ACD with the administration of Rux. In addition, the treatment of differentiating T cells with Rux downregulated the level of IL-2-mediated glycolysis in vitro. Furthermore, symptoms of ACD did not develop in T cell-specific Pgam1-deficient mice whose T cells had no glycolytic capacity. Taken together, our data suggest that the downregulation of glycolysis in T cells by Rux could be an important factor for the suppression of ACD development in mice.