{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:11:36Z","timestamp":1793293896066,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>T helper 2 (Th2)-mediated dermatoses are inflammatory skin diseases driven by CD4+ Th2 cells that produce interleukin (IL)-4, IL-5, IL-13, and IL-31, promoting immunoglobulin E (IgE) class switching, eosinophil recruitment, mast cell degranulation, and pruritus. We aimed to place these conditions in context and clarify how Th2 biology informs diagnosis and therapy. We conducted a narrative synthesis of mechanistic, translational, and clinical evidence on Th2 pathways in atopic dermatitis (AD), prurigo nodularis, bullous pemphigoid, chronic spontaneous urticaria, and selected type I\/IVb hypersensitivity reactions, with focused appraisal of trials targeting IL-4R\u03b1, IL-13, and IL-31R. Persistent Th2 activation is associated with epidermal barrier dysfunction, immune dysregulation, and pruritogenic neural signaling; AD is the archetype, showing prominent lesional IL-4\/IL-13 activity correlated with severity and itch. Across disorders, pathway-directed biologics against IL-4R\u03b1, IL-13, and IL-31R consistently reduce disease activity and pruritus in AD and prurigo nodularis, with emerging signals of benefit in bullous pemphigoid and chronic spontaneous urticaria. The Th2 axis provides a unifying pathogenic framework and actionable therapeutic target across multiple dermatoses. Integrating cytokine profiling with clinical phenotypes may refine patient stratification and optimize the deployment of existing and next-generation Th2-targeting therapies.<\/jats:p>","DOI":"10.3390\/ijms262110720","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:11:16Z","timestamp":1762254676000},"page":"10720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Central Role of Th2 Immune Response in Inflammatory Dermatoses: From Pathogenesis to Targeted Therapies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3504-2417","authenticated-orcid":false,"given":"Valentina","family":"Pala","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1655-0395","authenticated-orcid":false,"given":"Francois","family":"Rosset","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-3219","authenticated-orcid":false,"given":"Luca","family":"Mastorino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Sciamarrelli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Boskovic","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Borriello","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1915-9993","authenticated-orcid":false,"given":"Eleonora","family":"Bongiovanni","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9270-1204","authenticated-orcid":false,"given":"Orsola","family":"Crespi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-1406","authenticated-orcid":false,"given":"Simone","family":"Ribero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Quaglino","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Dermatology and Venereology, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.jaci.2011.01.053","article-title":"Contrasting pathogenesis of atopic dermatitis and psoriasis\u2014Part I: Clinical and pathologic concepts","volume":"127","author":"Nograles","year":"2011","journal-title":"J. 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