{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:30:20Z","timestamp":1785537020793,"version":"3.56.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030- 160196\/1"],"award-info":[{"award-number":["310030- 160196\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BBS\/E\/I\/00007039"],"award-info":[{"award-number":["BBS\/E\/I\/00007039"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Equine insect bite hypersensitivity (IBH) is the most common skin disease affecting horses. It is described as an IgE-mediated, Type I hypersensitivity reaction to salivary gland proteins of <jats:italic>Culicoides<\/jats:italic> insects. Together with Th2 cells, epithelial barrier cells play an important role in development of Type I hypersensitivities. In order to elucidate the role of equine keratinocytes in development of IBH, we stimulated keratinocytes derived from IBH-affected (IBH-KER) (n = 9) and healthy horses (H-KER) (n = 9) with <jats:italic>Culicoides<\/jats:italic> recombinant allergens and extract, allergic cytokine milieu (ACM) and a Toll like receptor ligand 1\/2 (TLR-1\/2-L) and investigated their transcriptomes. Stimulation of keratinocytes with <jats:italic>Culicoides<\/jats:italic> allergens did not induce transcriptional changes. However, when stimulated with allergic cytokine milieu, their gene expression significantly changed. We found upregulation of genes encoding for <jats:italic>CCL5<\/jats:italic>, <jats:italic>-11<\/jats:italic>, <jats:italic>-20<\/jats:italic>, <jats:italic>-27<\/jats:italic> and interleukins such as <jats:italic>IL31<\/jats:italic>. We also found a strong downregulation of genes such as <jats:italic>SCEL<\/jats:italic> and <jats:italic>KRT16<\/jats:italic> involved in the formation of epithelial barrier. Following stimulation with TLR-1\/2-L, keratinocytes significantly upregulated expression of genes affecting Toll like receptor and NOD-receptor signaling pathway as well as NF-kappa B signaling pathway, among others. The transcriptomes of IBH-KER and H-KER were very similar: without stimulations they only differed in one gene (<jats:italic>CTSL)<\/jats:italic>; following stimulation with allergic cytokine milieu we found only 23 differentially expressed genes (e.g. <jats:italic>CXCL10<\/jats:italic> and <jats:italic>11<\/jats:italic>) and following stimulation with TLR-1\/2-L they only differed by expression of seven genes. Our data suggests that keratinocytes contribute to the innate immune response and are able to elicit responses to different stimuli, possibly playing a role in the pathogenesis of IBH.<\/jats:p>","DOI":"10.1371\/journal.pone.0266263","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T18:59:09Z","timestamp":1659380349000},"page":"e0266263","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall?"],"prefix":"10.1371","volume":"17","author":[{"given":"Iva","family":"Cvitas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Oberhaensli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":true,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-4350","authenticated-orcid":true,"given":"Eliane","family":"Marti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"issue":"6","key":"pone.0266263.ref001","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.2042-3292.2004.tb00321.x","article-title":"Equine insect hypersensitivity","volume":"16","author":"RC Pilsworth","year":"2004","journal-title":"Equine Veterinary Education"},{"issue":"4","key":"pone.0266263.ref002","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.2042-3306.1990.tb04259.x","article-title":"Equine insect hypersensitivity: skin test and biopsy results correlated with clinical data","volume":"22","author":"VA Fadok","year":"1990","journal-title":"Equine veterinary journal"},{"issue":"3","key":"pone.0266263.ref003","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.2042-3306.1983.tb01788.x","article-title":"Sweet itch: responses of clinically normal and affected horses to intradermal challenge with extracts of biting insects","volume":"15","author":"PJ Quinn","year":"1983","journal-title":"Equine veterinary journal"},{"issue":"3\u20134","key":"pone.0266263.ref004","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.vetimm.2012.03.017","article-title":"Equine insect bite hypersensitivity: what do we know?","volume":"147","author":"A Schaffartzik","year":"2012","journal-title":"Veterinary immunology and immunopathology"},{"issue":"5","key":"pone.0266263.ref005","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/all.13722","article-title":"EAACI position paper: Comparing insect hypersensitivity induced by bite, sting, inhalation or ingestion in human beings and animals","volume":"74","author":"I Pali-Scholl","year":"2019","journal-title":"Allergy"},{"issue":"2","key":"pone.0266263.ref006","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.2042-3306.1984.tb01876.x","article-title":"Preferential landing and engorging sites of Culicoides species landing on a horse in Ireland","volume":"16","author":"P Townley","year":"1984","journal-title":"Equine veterinary journal"},{"issue":"3","key":"pone.0266263.ref007","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.2042-3306.1987.tb01389.x","article-title":"Allergic dermatitis (sweet itch) of Icelandic horses in Sweden: an epidemiological study","volume":"19","author":"H Brostrom","year":"1987","journal-title":"Equine veterinary journal"},{"issue":"7","key":"pone.0266263.ref008","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2746\/042516401776249444","article-title":"Immunoglobulin-E-bearing cells in skin biopsies of horses with insect bite hypersensitivity","volume":"33","author":"A van der Haegen","year":"2001","journal-title":"Equine veterinary journal"},{"issue":"1","key":"pone.0266263.ref009","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.vetimm.2009.09.011","article-title":"IgE in horses: occurrence in health and disease","volume":"132","author":"B. 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