{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Interleukin‑31 (IL‑31) is a cytokine predominantly produced by T‐helper type 2 cells—and, under inflammatory conditions, also by mast cells and dendritic cells—that has emerged as a central mediator linking immune activation to the neuroimmune manifestations of pruritic skin disorders. IL‑31 signals via a heterodimeric receptor complex composed of IL‑31 receptor A and the oncostatin M receptor β, which is expressed on a variety of cell types including sensory neurons, keratinocytes, and cells of the immune system."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " Activation of this receptor complex triggers downstream signaling pathways—including Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen‑activated protein kinase (MAPK) and phosphatidylinositol‑3‑kinase (PI3K) cascades—that lead to the production of pro‑inflammatory mediators and, importantly, to the direct stimulation of sensory neurons, evoking calcium mobilization and ERK phosphorylation that contribute to the generation of itch."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Elevated levels of IL‑31 have been documented in both adult and pediatric patients with atopic dermatitis, where its expression correlates with disease severity, pruritus, and impaired epidermal differentiation, thereby implicating IL‑31 not only as an effector of itch but also as a contributor to barrier dysfunction. Moreover, genetic studies have associated IL‑31 gene variants with nonatopic eczema, supporting the concept that dysregulated IL‑31 expression may drive the initiation and persistence of inflammatory skin lesions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings highlight IL‑31 as a critical player in the interplay between immune responses and skin homeostasis, making it a promising therapeutic target for the treatment of pruritus and inflammatory skin diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stacey R Dillon, Cindy Sprecher, Angela Hammond, et al. 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