title: Psoriasis and streptococci: the natural selection of psoriasis revisited.
abstract: We have previously postulated that surviving invasive streptococcal infections may have been a factor in psoriasis becoming a common skin disease in some parts of the world. Many of the candidate genes linked to psoriasis are associated with the acquired or innate immune system, which are also important in host defence to invasive streptococcal infections. High rates of positive streptococcal throat swabs among patients with chronic plaque psoriasis suggest that they are efficient at internalizing/carrying beta-haemolytic streptococci. Internalization of streptococci in the throat is dependent upon the transforming growth factor (TGF)-beta/fibronectin/alpha 5 beta 1 integrin pathway. The immune cell Th17 and its related cytokine network are important in mucosal defence, being very effective against extracellular microbes but having little effect on intracellular organisms. The TGF-beta/fibronectin/alpha 5 beta 1 integrin pathway and the Th17 cell network also appear to be operative in psoriasis, animal models of both TGF-beta and alpha 5 beta 1 cutaneous overexpression being associated with characteristic psoriasis lesions. We postulate that some of the genotypic/phenotypic changes in different immunological pathways in psoriasis, including the acquired T-cell response, the innate immune response, the TGF-beta/fibronectin/alpha 5 beta 1 integrin pathway and the Th17 cell system, confer protection against mortality during epidemics of invasive streptococcal infections, heightened efficiency in internalizing and allowing carriage of streptococci as well as predisposition to the development of psoriasis.
authors.affiliation: Department of Cutaneous Allergy, St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, UK. john.mcfadden@kcl.ac.uk
authors.forename: J P
authors.initials: JP
authors.lastname: McFadden
authors.forename: B S
authors.initials: BS
authors.lastname: Baker
authors.forename: A V
authors.initials: AV
authors.lastname: Powles
authors.forename: L
authors.initials: L
authors.lastname: Fry
mesh_terms: D004196:Disease Outbreaks; D006801:Humans; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D012641:Selection, Genetic; D013290:Streptococcal Infections / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology
chemical_list: D016212:Transforming Growth Factor beta