title: Reducing Flightless I expression decreases severity of psoriasis in an imiquimod-induced murine model of psoriasiform dermatitis.
abstract: BACKGROUND
  Psoriasis is a common chronic skin condition characterized by excessive inflammation and aberrant epidermal proliferation. Flightless I (Flii) is an actin-remodelling protein that regulates these processes, suggesting a possible role in psoriasis.
  
  
  OBJECTIVE
  We sought to determine whether a benefit in psoriasiform dermatitis might occur after modulating Flii gene expression or reducing its levels using neutralizing antibodies.
  
  
  METHODS
  Biopsies of psoriatic skin lesions from patients were assessed for Flii levels. Psoriasis-like lesions were induced in Flii heterozygous (Flii+/-), wild-type (Flii+/+) and Flii transgenic (FliiTg/Tg) mice using topical application of imiquimod. Additionally, psoriasis-induced wild-type mice were treated with topical application of Flii neutralizing antibodies and erythema, inflammation and histology were assessed.
  
  
  RESULTS
  Flii was elevated in psoriatic lesions from patients with psoriasis compared with normal human skin. Reducing Flii decreased erythema, inflammatory cell infiltrate, proinflammatory cytokines and the thickness of the epidermis. Topical application of Flii neutralizing antibodies to wild-type mice treated with imiquimod resulted in significantly reduced psoriasiform dermatitis.
  
  
  CONCLUSIONS
  Flii is a novel target involved in psoriasiform dermatitis and reducing cutaneous Flii could potentially be a new approach for treating patients with psoriasis.
authors.affiliation: Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.|School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: H T
authors.initials: HT
authors.lastname: Chong
authors.affiliation: Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: G N
authors.initials: GN
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Sidhu
authors.affiliation: Surgical Pathology Division, South Australia Pathology, Adelaide, South Australia, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Ibbetson
authors.affiliation: Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.|School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Z
authors.identifier: http://orcid.org/0000-0002-8072-4222
authors.initials: Z
authors.lastname: Kopecki
authors.affiliation: Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.|School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cowin
mesh_terms: D000279:Administration, Cutaneous; D000634:Aminoquinolines / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D003875:Drug Eruptions / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins; D008875:Middle Aged; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015534:Trans-Activators
chemical_list: D000634:Aminoquinolines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C000609263:FlII protein, mouse; D007509:Irritants; D008840:Microfilament Proteins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D015534:Trans-Activators; D000077271:Imiquimod