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Research suggests that T\u2010cell exhaustion, increased immunosuppressive cytokines, induction of regulatory T cells and increased expression of immune checkpoint inhibitors may contribute to its pathogenesis. This study aimed to gain a deeper understanding of the molecular changes occurring in canine demodicosis using mass spectrometry and pathway enrichment analysis. The results indicate that endoplasmic reticulum stress promotes canine demodicosis through regulation of three linked signalling pathways: eIF2, mTOR, and eIF4 and p70S6K. These pathways are involved in the modulation of Toll\u2010like receptors, most notably TLR2, and have been shown to play a role in the pathogenesis of skin diseases in both dogs and humans. Moreover, these pathways are also implicated in the promotion of immunosuppressive M2 phenotype macrophages. Immunohistochemical analysis, utilising common markers of dendritic cells and macrophages, verified the presence of M2 macrophages in canine demodicosis. The proteomic analysis also identified immunological disease, organismal injury and abnormalities and inflammatory response as the most significant underlying diseases and disorders associated with canine demodicosis. This study demonstrates that\n                    <jats:italic>Demodex<\/jats:italic>\n                    mites, through ER stress, unfolded protein response and M2 macrophages contribute to an immunosuppressive microenvironment, thereby assisting in their proliferation.\n                  <\/jats:p>","DOI":"10.1111\/pim.13033","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T09:48:30Z","timestamp":1712915310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unveiling the Role of Endoplasmic Reticulum Stress Pathways in Canine Demodicosis"],"prefix":"10.1111","volume":"46","author":[{"given":"Pamela A.","family":"Kelly","sequence":"first","affiliation":[{"name":"UCD School of Veterinary Medicine University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-0041","authenticated-orcid":false,"given":"Gillian P.","family":"McHugo","sequence":"additional","affiliation":[{"name":"UCD School of Agriculture and Food Science University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitriona","family":"Scaife","sequence":"additional","affiliation":[{"name":"Proteomics Core, Mass Spectrometry Resource UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Peters","sequence":"additional","affiliation":[{"name":"UCD School of Veterinary Medicine University College Dublin  Dublin 4 Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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