{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have consistently identified PHF11 as a susceptibility gene in atopic and immunoglobulin E–mediated diseases such as asthma and atopic dermatitis. The PHF11 gene encodes a protein harboring two plant homeodomain (PHD) zinc finger motifs—domains typically involved in transcriptional regulation—and produces distinctive splice variants expressed in immune tissues. Replicated association studies across diverse populations have linked PHF11 variants with elevated serum IgE levels and increased disease severity, highlighting its potential role in the modulation of atopic phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these genetic associations, functional analyses in T lymphocytes have elucidated a more direct role for PHF11 in the regulation of immune responses. In activated T cells, PHF11 functions as a transcriptional co‐activator for key Th1 cytokine genes—most notably interferon‑γ (IFNG) and interleukin‑2 (IL2)—by enhancing the nuclear import and DNA binding capacity of nuclear factor kappa B (NF‑κB) at the IFNG promoter. Experimental knock‐down of PHF11 leads to decreased transcription of these cytokines, reduced CD28 expression, and impaired expression of other regulatory genes essential for T-cell viability and homeostasis, thereby underscoring a broad role in T-cell activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDespite the robust evidence linking PHF11 to atopic disorders, studies in certain ethnic cohorts have revealed variable association strengths, suggesting that its contribution to disease susceptibility may depend on complex interactions between genetic background and environmental exposures. These observations call for further mechanistic investigations to fully elucidate how PHF11–mediated transcriptional regulation impacts immune function and the pathogenesis of atopic diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Youming Zhang, Nicholas I Leaves, Gavin G Anderson, et al. 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