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Airborne stimuli activate the mucosal epithelium to release a number of molecules impacting the activity of resident immune and environmental cells. Signals from the mucosal barrier, regulatory cells, and the inflamed tissue are crucial conditions able to modify innate and adaptive effector cells providing the selective homing of eosinophils or neutrophils. The high plasticity of resident T\u2010 and innate lymphoid cells responding to external signals is the prerequisite to explain the multiplicity of endotypes of allergic diseases. This notion paved the way for the huge use of specific biologic drugs interfering with pathogenic mechanisms of inflammation. Based on the response of the epithelial barrier, the activity of resident regulatory cells, and functions of structural non\u2010lymphoid environmental cells, this review proposes some immunopathogenic scenarios characterizing the principal endotypes which can be associated with a precise phenotype of asthma. Recent literature indicates that similar concepts can also be applied to the inflammation of other non\u2010respiratory allergic disorders. The next challenges will consist in defining specific biomarker(s) of each endotype allowing for a quick diagnosis and the most effective personalized therapy.<\/jats:p>","DOI":"10.1111\/all.15445","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T05:08:10Z","timestamp":1658034490000},"page":"3267-3292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A pathogenic integrated view explaining the different endotypes of asthma and allergic disorders"],"prefix":"10.1111","volume":"77","author":[{"given":"Enrico","family":"Maggi","sequence":"first","affiliation":[{"name":"Department of Immunology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Parronchi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Giuseppe","family":"Azzarone","sequence":"additional","affiliation":[{"name":"Department of Immunology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Moretta","sequence":"additional","affiliation":[{"name":"Department of Immunology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.02.016"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15230"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1988.tb05045.x"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830180712"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115300"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.10.4538"},{"issue":"4","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.4049\/jimmunol.146.4.1169","article-title":"Accumulation of Th\u20102\u2010like helper T cells in the conjunctiva of patients with vernal conjunctivitis","volume":"146","author":"Maggi E","year":"1991","journal-title":"J Immunol."},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.018"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000800"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2032506"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.05.052"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.06.006"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1892"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.07.062"},{"key":"e_1_2_13_16_1","unstructured":"Global Initiative for Asthma (GINA).Global strategy for asthma management and prevention\u2014updated 2016.2016. 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