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Furthermore, increased expression of toll\u2010like receptor 2 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2) has been identified in rosacea skin supporting the participation of the innate immune system. Notably, <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>s are expressed on sensory neurons and increase neuronal excitability linking <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> signalling to the transmission of neuroinflammatory responses. It is the intention of this viewpoint to present a unifying concept that links all known clinical trigger factors of rosacea such as <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation, heat, skin irritants and special foods to one converging point: enhanced endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) stress that activates the unfolded protein response (<jats:styled-content style=\"fixed-case\">UPR<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress via upregulation of transcription factor <jats:styled-content style=\"fixed-case\">ATF<\/jats:styled-content>4 increases <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2 expression, resulting in enhanced production of cathelicidin and <jats:styled-content style=\"fixed-case\">KLK<\/jats:styled-content>5 mediating downstream proinflammatory, angiogenic and antimicrobial signalling. The presented concept identifies rosacea trigger factors as environmental stressors that enhance the skin's <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress response. Exaggerated cutaneous <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress that stimulates the <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>2\u2010driven inflammatory response may involve sebocytes, keratinocytes, monocyte\u2010macrophages and sensory cutaneous neurons. Finally, all antirosacea drugs are proposed to attenuate the <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress signalling cascade at some point. Overstimulated <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress signalling may have evolutionarily evolved as a compensatory mechanism to balance impaired vitamin D\u2010driven <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037\u2010mediated antimicrobial defenses due to lower exposure of <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content>\u2010B irradiation of the northern Celtic population.<\/jats:p>","DOI":"10.1111\/exd.12517","type":"journal-article","created":{"date-parts":[[2014,7,21]],"date-time":"2014-07-21T14:25:30Z","timestamp":1405952730000},"page":"868-873","source":"Crossref","is-referenced-by-count":49,"title":["Endoplasmic reticulum stress: key promoter of rosacea pathogenesis"],"prefix":"10.1111","volume":"23","author":[{"given":"Bodo C.","family":"Melnik","sequence":"first","affiliation":[{"name":"Department of Dermatology, Environmental Medicine and Health Theory University of Osnabr\u00fcck 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