{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:53:03Z","timestamp":1791363183621,"version":"4.3.1"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by a combination of genetic predisposition, epidermal barrier dysfunction, immune dysregulation, aberrant neuroinflammatory signaling, and environmental factors. Genetic defects in barrier-related molecules, particularly loss-of-function mutations in filaggrin (FLG), represent key heritable determinants of impaired epidermal integrity and enhanced allergen penetration. In recent years, advances in the understanding of its molecular pathogenesis have progressively shifted the therapeutic paradigm from conventional broad-spectrum immunosuppression toward precision-targeted interventions aimed at key inflammatory pathways, substantially transforming disease management in patients with moderate-to-severe AD. Current evidence indicates that type 2 immune inflammation remains a central pathogenic axis in AD. Key mediators, including interleukin (IL)-4, IL-13, IL-31, thymic stromal lymphopoietin (TSLP), and the Janus kinase (JAK)\u2013signal transducer and activator of transcription (STAT) signaling pathway, collectively contribute to epidermal barrier disruption, inflammatory amplification, and the itch\u2013scratch cycle. Based on these mechanisms, a range of biologics and small-molecule targeted therapies\u2014including IL-4 receptor \u03b1 (IL-4R\u03b1) antagonists, IL-13 monoclonal antibodies, IL-31 pathway inhibitors, JAK inhibitors, and emerging OX40\/OX40L modulatory strategies\u2014have demonstrated significant efficacy in randomized controlled trials and real-world studies, thereby ushering AD into a mechanism-driven therapeutic era. However, targeted therapies still face critical challenges, including heterogeneous treatment responses, insufficient long-term safety data, limited stratification of disease endotypes, and disparities in treatment accessibility. Increasing evidence suggests that therapeutic response is more closely associated with immunological endotypes than traditional clinical phenotypes, and that single-pathway blockade alone is insufficient to achieve durable disease modification. This review systematically summarizes the key pathogenic mechanisms of AD, current targeted therapeutic strategies, and their clinical translation progress, with a particular focus on existing therapeutic challenges and future directions. Ultimately, integration of biomarkers, multi-omics profiling, real-world evidence, and artificial intelligence\u2013assisted decision-making may facilitate the development of endotype-based precision treatment frameworks, enabling a shift from disease control toward sustained remission and true disease modification.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1959035","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:32:50Z","timestamp":1791361970000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted therapies in atopic dermatitis: toward endotype-driven precision medicine and disease modification"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei","family":"Song","sequence":"first","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Lishui Traditional Chinese Medicine Hospital","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Yao","sequence":"additional","affiliation":[{"name":"Lishui Central Hospital, Shaoxing University","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzhen","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Gongji Gastrointestinal Tumor Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiya","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Lishui Traditional Chinese Medicine Hospital","place":["Lishui, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.12.1124","article-title":"Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities","volume":"127","author":"Su\u00e1rez-Fari\u00f1as","year":"2011","journal-title":"J Allergy Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.08.031","article-title":"Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study","volume":"132","author":"Silverberg","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0091-6749(99)70536-1","article-title":"Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies 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