{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KLRC4 (also known as NKG2F) is a member of the NKG2 family of C‐type lectin receptors that is expressed on natural killer (NK) cells and modulates innate immune responses. Multiple genetic studies have demonstrated that polymorphisms in KLRC4 are associated with susceptibility to immune‐mediated diseases such as Behçet’s disease, supporting its role in the regulation of inflammatory processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, a missense variant in KLRC4 has been linked to clinical outcomes in chronic lymphocytic leukemia, suggesting a prognostic relevance in malignancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, investigation of NK receptor polymorphisms in the context of chronic hepatitis B has explored KLRC4’s potential contribution to antiviral immunity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while parallel expression studies have measured KLRC4 transcript levels in patients with inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional analyses indicate that KLRC4 expression on peripheral blood NK cells is inducible upon cytokine stimulation (e.g., with interleukin-2 or interleukin-15), which supports its role in promoting NK cell activation and cytotoxic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, its inclusion in diagnostic and prognostic gene expression signatures for conditions such as myocardial infarction and lung squamous cell carcinoma underscores its potential use as a biomarker reflecting the status of NK cell–driven immunity in varied pathological settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, current evidence suggests that KLRC4 contributes to fine-tuning NK cell activation and immune surveillance. Its genetic variants not only affect disease susceptibility in inflammatory and neoplastic conditions but also serve as potential biomarkers for NK cell functionality, thereby providing new insights into innate immune regulation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yohei Kirino, George Bertsias, Yoshiaki Ishigatsubo, et al. 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