title: Deficiency of IL-22 contributes to a chronic inflammatory disease: pathogenetic mechanisms in acne inversa.
abstract: Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-γ, IL-24, or IL-1β. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and -inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10-inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, D-10117 Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Warszawska
authors.forename: Conny
authors.initials: C
authors.lastname: Hoeflich
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.forename: Sylke
authors.initials: S
authors.lastname: Schneider-Burrus
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kunz
authors.forename: Annette
authors.initials: A
authors.lastname: Buss
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Roewert
authors.forename: Markus
authors.initials: M
authors.lastname: Krause
authors.forename: Ansgar
authors.initials: A
authors.lastname: Lukowsky
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000172:deficiency / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000172:deficiency; D005260:Female; D017497:Hidradenitis Suppurativa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D007378:Interleukins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D015854:Up-Regulation / Q000276:immunology; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D000097043:Interleukin-22