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.