The H3K9 demethylase plant homeodomain finger protein 2 regulates interleukin 4 production in CD4+ T cells

•Plant homeodomain finger protein 2 (PHF2) affects IL-4 production in CD4+ T cells.•PHF2 may be involved in the progression of atopic dermatitis.•PHF2 represents a therapeutic target in Th2-mediated allergic diseases. CD4+ T cells play a key role in the immune response via their differentiation into various helper T cell subsets that produce characteristic cytokines. Epigenetic changes in CD4+ T cells are responsible for cytokine production in these subsets, although the exact molecular mechanisms remain unclear. Therefore, we investigated the effects of plant homeodomain finger protein 2 (PHF2), a histone H3K9 demethylase, on cytokine production in CD4+ T cells using T cell-specific Phf2-conditional knockout (cKO) mice in this study. we showed that interleukin 4 (Il4) expression was significantly decreased in Phf2-cKO CD4+ T cells compared to that in wild-type cells. To further elucidate the role of PHF2 in vivo, we assessed immune responses in a mouse model of ovalbumin (OVA)-induced atopic dermatitis. Phf2-cKO mice exhibited lower serum levels of OVA-specific IgE than those in wild-type mice. These findings suggest that PHF2 plays a role in promoting T helper 2 cell (Th2) function and may contribute to the pathogenesis of Th2-related allergies such as atopic dermatitis. This study demonstrated the impact of PHF2 on cytokine production in CD4+ T cells for the first time. Further studies on the PHF2-mediated epigenetic mechanisms may lead to the development of treatments for a variety of immune diseases.