The effect of parental T-cell deficiency on offspring response to skin inflammation 9386

Abstract Description Offspring phenotypes are not only transmitted to the next generation through the DNA code but also through germ cell epigenetic modifications induced by the environment encountered by previous generations. For example, the impact of parental diet and stress on offspring metabolic phenotypes have been well studied. In addition, we have previously shown that the absence of T cells in parents can lead to the epigenetic transmission of certain skin phenotypes across multiple generations. Here, we investigated how parental T cell deficiency influences the offspring skin immune response, despite T cell sufficiency in the offspring. To assess the role of parental T cell deficiency in skin immune response, we employed a mouse model of atopic dermatitis induced by topical application of the Vitamin D3 analog, MC903. Progeny that were generated from a T cell-deficient male crossed to a wildtype female mouse displayed significantly reduced MC903-induced ear inflammation, which correlated with a reduced number of Th17 and Th2 T cells, along with an increased frequency of regulatory T cells in the ear skin. The reduced skin inflammation was observed in both male and female progeny and also in progeny generated from a WT male crossed to a T cell-deficient female. Furthermore, the phenotype persisted even in the F2 generation, independent of their genotype. These data suggest that T cell deficiency in either parent, can non-genetically influence the offspring skin immune response. Funding Sources Supported by NHLBI Hematology Research T32 Topic Categories Mucosal and Regional Immunology (MUC)