{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:46:45Z","timestamp":1792630005192,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Conjunctival intraepithelial lymphocytes, tear soluble molecules and commensal microbiota have important roles in the ocular mucosal immune response in healthy and diseased subjects. For the purpose of this study, the cellular and microbial populations of the conjunctiva and the lacrimal soluble molecules were analyzed to find the main biomarkers in allergic conjunctivitis. A total of 35 healthy subjects, 28 subjects with seasonal allergic conjunctivitis and 32 subjects with perennial allergic conjunctivitis were recruited to obtain peripheral blood, conjunctival brush cytology, tear fluid and microbiota samples. Flow cytometry for lymphocytes, multiplex bead assays for cytokines and high-throughput DNA sequencing for microbiome analysis were used. For perennial allergic conjunctivitis, an increased proportion of Th2 and NKT lymphocytes was found, while CD3+TCR\u03b3\u03b4+ lymphocytes and double negative MAIT cells were decreased. In contrast, seasonal allergic conjunctivitis was distinguished by an increase in Th17 and Th22 cell proportions, while the Th1 cell proportion decreased. Among tear fluid, the vast majority of pro-inflammatory cytokines (especially Th2 and Th17 cytokines) in perennial allergies and MMP-9 together with IgA in seasonal allergies were increased. In contrast, TGF-\u03b22 was decreased in both forms of conjunctivitis. Finally, fungal (<jats:italic>Malassezia<\/jats:italic>species) and bacterial (<jats:italic>Kocuria<\/jats:italic>and<jats:italic>Propionobacterium acnes<\/jats:italic>species) colonization were observed in the perennial allergic conjunctivitis group. These results provide the basis for the development of a disease profile for perennial allergic conjunctivitis and open the door to new therapeutic and diagnostic strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2022.911022","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T08:16:51Z","timestamp":1658218611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":35,"title":["Conjunctival Intraepithelial Lymphocytes, Lacrimal Cytokines and Ocular Commensal Microbiota: Analysis of the Three Main Players in Allergic Conjunctivitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jos\u00e9 Carlos","family":"Zarzuela","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Reinoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Armentia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Enr\u00edquez-de-Salamanca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Corell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e32834a9676","article-title":"Epidemiology of Allergic Conjunctivitis","volume":"11","author":"Rosario","year":"2011","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000299","article-title":"An Update on Ocular Allergy","volume":"16","author":"Shaker","year":"2016","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2000.00699.x","article-title":"Tear Levels of Interferon-Gamma, Interleukin (IL) -2, IL-4 and IL-5 in Patients With Vernal Keratoconjunctivitis, Atopic Keratoconjunctivitis and Allergic Conjunctivitis","volume":"30","author":"Uchio","year":"2000","journal-title":"Clin Exp Allergy"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.4.4.457","article-title":"Cytokines and Chemokines in Immune-Based Ocular Surface Inflammation","volume":"4","author":"Enr\u00edquez-de-Salamanca","year":"2008","journal-title":"Expert Rev Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-006-0285-7","article-title":"Th1- and Th2-Type Cytokines in Chronic Ocular Allergy","volume":"244","author":"Leonardi","year":"2006","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.27","article-title":"Topographical Distribution and Characterization of Epithelial Cells and Intraepithelial Lymphocytes in the Human Ocular Mucosa","volume":"5","author":"Reinoso","year":"2012","journal-title":"Mucosal Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6917185","article-title":"The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis","volume":"2020","author":"Meng","year":"2020","journal-title":"J Ophthalmol"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.146.4.1169","article-title":"Accumulation of Th-2-Like Helper T Cells in the Conjunctiva of Patients With Vernal Conjunctivitis","volume":"146","author":"Maggi","year":"1991","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq046","article-title":"NKT Cells are Necessary for Maximal Expression of Allergic Conjunctivitis","volume":"22","author":"Reyes","year":"2010","journal-title":"Int Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8071033","article-title":"Current Evidence on the Ocular Surface Microbiota and Related Diseases","volume":"8","author":"Petrillo","year":"2020","journal-title":"Microorganisms"},{"key":"B11","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.immuni.2017.06.014","article-title":"An Ocular Commensal Protects Against Corneal Infection by Driving an Interleukin-17 Response From Mucosal \u03b3\u03b4 T Cells","volume":"47","author":"St Leger","year":"2017","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000559","article-title":"Role of the Ocular Surface Microbiome in Allergic Disease","volume":"19","author":"Cavuoto","year":"2019","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B13","unstructured":"LahtiL SurdarshanS Microbiome R Package. 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