Ten-eleven translocation 2 modulates allergic inflammation by 5-hydroxymethylcytosine remodeling of immunologic pathways.

Allergic rhinitis (AR) is an allergen specific IgE-mediated inflammatory disease. Both genetic and environmental factors could play a role in the pathophysiology of AR. 5-methylcytosine (5-mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the Ten-Eleven Translocation (TET) family of proteins as part of active DNA de-methylation pathway. 5hmC plays an important role in regulation of gene expression and differentiation in immune cells. Here we show that loss of ten-eleven translocation protein 2 (Tet2) could impact the severity of AR in the ovalbumin-induced mouse model. Genome-wide 5hmC profiling of both wildtype and Tet2 KO mice in response to AR revealed that the loss of Tet2 could lead to 5hmC alteration at specific immune response genes. Both partial loss and complete loss of Tet2 alters the 5hmC dynamic remodeling for the adaptive immune pathway, as well as cytokines. Thus, our results reveal a new role of Tet2 in immunology, and Tet2 may serve as a promising target in regulating the level of immune response.