{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nInterleukin‐4–induced gene 1 (IL4I1) is a secreted l‐amino acid oxidase originally identified as an early IL‐4–inducible gene that exerts diverse immunoregulatory functions. IL4I1 can inhibit both CD4 and CD8 T‐cell activation and proliferation through its enzymatic conversion of amino acids to products such as hydrogen peroxide, leading to down‐regulation of T‐cell receptor components and fostering an immunosuppressive microenvironment. Moreover, IL4I1 expression in macrophages drives polarization toward the anti‐inflammatory M2 phenotype via activation of signaling pathways including STAT3 and STAT6, thereby shaping adaptive immune responses and facilitating tumor escape in certain cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in modulating T‐cell activity, IL4I1 also influences other arms of the immune system. In the central nervous system, for example, IL4I1 secreted by alternatively activated macrophages contributes to inflammation resolution and remyelination by suppressing proinflammatory cytokine (e.g., IFN‐γ and IL‐17) expression. In the adaptive B‐cell compartment, IL4I1 serves as a negative regulator by restraining B‐cell receptor signaling, thus influencing B‐cell egress and the generation of antibody responses. In addition, IL4I1 shapes CD8 T‐cell priming by reducing the stability of T cell–dendritic cell immune synapses, thereby increasing the threshold for activation and favoring the expansion of high-affinity effector clones while limiting long-lived memory formation. Notably, studies in prostate adenocarcinoma cells have paralleled the concept that enzymes catalyzing amino acid oxidation (including selenoproteins such as SELV and SELW) contribute to the cellular redox state and may influence tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, IL4I1 expression is itself subject to epigenetic regulation. In inflammatory contexts such as acute lung injury, modulation of histone methylation by enzymes like JMJD3 affects IL4I1 levels, thereby influencing the macrophage M1/M2 balance and the overall inflammatory response. In cutaneous melanoma, increased IL4I1 expression by B‐cell subsets augments IL-10 production and impairs B‐cell trafficking, further reinforcing tumor‐associated immunosuppression. In parallel, studies on related enzymes such as LAO1 underscore that amino acid oxidases consistently impact inflammatory and metabolic homeostasis within diverse tissues, emphasizing the broader relevance of these oxidative mechanisms in immune regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroeki Sahara, Nilabh Shastri "}, {"type": "b", "children": [{"type": "t", "text": "Second class minors: molecular identification of the autosomal H46 histocompatibility locus as a peptide presented by major histocompatibility complex class II molecules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20021961"}], "href": "https://doi.org/10.1084/jem.20021961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12566421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12566421"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fanette Lasoudris, Céline Cousin, Armelle Prevost-Blondel, et al. 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