An Essential Role for RXRα in the Development of Th2 Responses

The study identified a hypomorphic allele of the Rxrα gene, RxrαPke, which caused a 90% loss of RXRα activity, leading to a progressive immunologic defect characterized by a skewed Th1 response and impaired Th2 differentiation. Homozygous RxrαPke mice exhibited premature graying, alopecia, and skin abnormalities. The mutation resulted in increased IL-12 production by dendritic cells and decreased suppressive activity of Treg cells, favoring a Th1-dominant immune response. The study concluded that RXRα is essential for Th2 differentiation and immune balance, acting indirectly by suppressing Th1 differentiation and IL-12 production.