{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n IL1F10, also known as interleukin‑38 (IL‑38), is a recently characterized member of the IL‑1 cytokine family that appears to function predominantly as an anti‐inflammatory regulator. Several studies have demonstrated that IL‑38 can bind to receptors including the IL‑36 receptor and IL‑1 receptor accessory proteins (e.g. IL‑1RAPL1), thereby modulating downstream inflammatory signaling cascades and cytokine production (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " For example, in experimental arthritis models, overexpression of IL‑38 in joint tissues reduced macrophage infiltration and attenuated the expression of pro‐inflammatory cytokines such as IL‑17, IL‑23, and TNFα, indicating that augmenting IL‑38 levels can limit inflammatory damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, studies in systemic lupus erythematosus have shown that endogenous IL‑38 functions to restrain the production of inflammatory mediators in peripheral blood mononuclear cells, suggesting a protective role in autoimmune pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, in psoriasiform skin inflammation, IL‑38 has been found to dampen IL‑17 production from activated γδ T cells via its interaction with IL‑1RAPL1, thereby contributing to the resolution of local inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic studies have also implicated IL1F10 in immune‐mediated inflammatory disorders. Polymorphisms within the IL1F10 locus have been associated with increased susceptibility to disorders such as ankylosing spondylitis and psoriatic arthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these data support a model in which IL1F10/IL‑38 acts as a natural immune regulator by competing with pro‑inflammatory ligands for receptor binding and suppressing the activation of downstream cytokine networks. Such anti‑inflammatory properties make IL1F10 a promising candidate for therapeutic exploitation in various autoimmune and inflammatory diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Frank L van de Veerdonk, Angela K Stoeckman, Gouping Wu, et al. 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