{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:04:24Z","timestamp":1780639464386,"version":"3.54.1"},"reference-count":158,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009857","name":"Regeneron Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Atopic diseases arise from an immunological imbalance where regulatory mechanisms are unable to preserve or restore homeostasis, leading to chronic inflammatory conditions affecting epithelial organs. This may involve homeostasis, deficient or insufficient regulatory T cells (Tregs) or other aberrant regulatory mechanisms. Type 2 (T2) immunity is a conserved response that evolved to combat large helminth parasites (worms), venoms, and toxins involving both innate and adaptive immune pathways. Many T2 cytokines and alarmins act to recruit and activate innate and adaptive immune cells, and they also lead to mucous production, hyperplasia, and tissue remodeling. These responses were designed to enhance expulsion of parasites, repair the barrier and elicit protective mechanical reflexes such as scratching or coughing. Today, with reduced parasitic exposure serving as an opposing influence on T2 immunity, it is hypothesized that T2 responses may be triggered by low amounts of environmental stimuli in genetically susceptible individuals, leading to unchecked T2 inflammation and atopic diseases at multiple barrier surfaces. This paper reviews the evidence linking host T2 immunity with T2 inflammatory mechanisms in atopic diseases and explores the hypothesis that these diseases may be perpetuated from a central imbalance between Th2 vs. Th1, Th3, and Tregs, influenced by tissue-dependent, local environmental-insult-driven innate cell responses, interconnected by a cycle of self-amplifying cytokine signaling.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1793641","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:37:36Z","timestamp":1780637856000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Restoring balance in atopic disorders: insights into type 2 immunity and chronic inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Eric L.","family":"Simpson","sequence":"first","affiliation":[{"name":"Department of Dermatology, Oregon Health & Science University","place":["Portland, OR, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Palomares","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus F.","family":"Rabe","sequence":"additional","affiliation":[{"name":"LungenClinic Grosshansdorf (member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN)","place":["Grosshansdorf, Germany"]},{"name":"Christian-Albrechts University (member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN)","place":["Kiel, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamo","family":"Deniz","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals","place":["Tarrytown, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Martin","sequence":"additional","affiliation":[{"name":"Sanofi","place":["Vernier, 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