The Loss of H3K27 Histone Demethylase Utx in T Cells Aggravates Allergic Contact Dermatitis.

The pathogenesis of allergic contact dermatitis (ACD) requires the activation of Ag-specific T cells, including effector and regulatory T cells. The differentiation and function of these T cells is epigenetically regulated through DNA methylation and histone modifications. However, the roles of altered histone H3K27 methylation in T cells in the development of ACD remain unknown. Two types of histone H3K27 demethylases, Utx and Jmjd3, have been reported in mammals. To determine the role of the histone H3K27 demethylase expression of T cells in the development of ACD, we generated T cell-specific, -deficient ( KO) mice or -deficient ( KO) mice. Unlike control mice, KO mice had severer symptoms of ACD, whereas KO mice showed symptoms identical to those in control mice. In KO mice with ACD, the massive infiltration of myeloid cells, including neutrophils and dendritic cells, has been observed. In addition, the expression of proinflammatory cytokines in CD4 T cells of the draining lymph nodes (LNs) and in CD8 T cells of the skin was increased in KO mice, whereas the ratio of Foxp3 regulatory CD4 T cells to Foxp3 conventional CD4 T cells was decreased in both the draining LNs and the skin of KO mice with ACD. Furthermore, Foxp3 regulatory CD4 T cells of KO mice with ACD expressed a decreased level of CCR4 (a skin-tropic chemokine receptor) in comparison with control. Thus, in CD4 T cells, could potentially be involved in the regulation of the pathogenesis of ACD.