A role for the atopy‐associated gene PHF11 in T‐cell activation and viability

Polymorphisms within plant homeodomain finger protein 11 (PHF11) are associated with total IgE, allergic asthma and eczema. PHF11 is a transcriptional co‐activator of the Th1 effector cytokine genes, interleukin‐2 (IL2) and interferon‐γ (IFNG), co‐operating with nuclear factor kappa B (NF‐κB). The involvement with NF‐κB led us to test whether PHF11 might have a broader function in T‐cell activation and viability. We show that PHF11 is abundant in the cytoplasm of T‐cells and imported into the nucleus of activated T‐cells. Consistent with its presence in the nucleus, PHF11 was recruited to the IFNG promoter and over‐expression of PHF11 increased the binding of NF‐κB to the IFNG promoter and IFNG gene transcription. Over‐expression of PHF11 did not increase IL2 gene transcription, suggesting some specificity in promoter recognition. In contrast, small‐interfering RNA knock‐down of PHF11 decreased transcription of both IFNG and IL2 and led to decreased CD28 cell‐surface expression and reduced NF‐κB nuclear import and DNA binding. Knock‐down of PHF11 also decreased cell viability and was accompanied by reduced expression of GIMAP4 and 5 genes required for T‐cell differentiation, viability and homeostasis. Therefore, in addition to its earlier identified function in regulating Th1 cytokine gene expression, we now show that PHF11 has a broader function in contributing to T‐cell activation and viability.