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Appropriate <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling is of pivotal importance for maintaining the inner and outer root sheath of the hair follicle and skin appendages. This viewpoint on the pathogenesis of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> is primarily supported by circumstantial evidence derived from translational biology. Impaired <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling is proposed to be the major pathogenic mechanism of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>. Deficient <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling switches the fate of outer root sheath cells, resulting in conversion of hair follicles to keratin\u2010enriched epidermal cysts. Impaired <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling may compromise apocrine gland homoeostasis as well. Damage\u2010associated molecular pattern molecules released by either ruptured epidermal cysts exposing keratin fibres or altered structural components of less maintained apocrine glands may both stimulate <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u2010mediated innate immunity. All aggravating factors of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>, that is, smoking, obesity, skin occlusion, androgens and progesterone, may further promote inflammation by release of proinflammatory cytokines derived from activated monocyte\/macrophages. Inappropriate <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling may not only initiate inflammation in <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> but may lead to insufficient feedback inhibition of overstimulated innate immunity. Regular <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling via induction of <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> phosphatase\u20101 (<jats:styled-content style=\"fixed-case\">MKP<\/jats:styled-content>\u20101) terminates <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>\u2010signalling in macrophages and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201023 secreting <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content>s, the key players for Th17 cell polarization. Thus, impaired <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch signalling links <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> to other Th17\u2010driven comorbidities. All major therapeutic interventions in <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> appear to attenuate increased <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activation of innate immune cells due to impaired Notch\u2010mediated feedback regulation of innate immunity.<\/jats:p>","DOI":"10.1111\/exd.12098","type":"journal-article","created":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T18:37:51Z","timestamp":1359139071000},"page":"172-177","source":"Crossref","is-referenced-by-count":132,"title":["Impaired Notch\u2010<scp>MKP<\/scp>\u20101 signalling in hidradenitis suppurativa: an approach to pathogenesis by evidence from translational biology"],"prefix":"10.1111","volume":"22","author":[{"given":"Bodo C.","family":"Melnik","sequence":"first","affiliation":[{"name":"Department of Dermatology Environmental Medicine and Health Theory University of Osnabr\u00fcck Osnabr\u00fcck 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