title: Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse.
abstract: BACKGROUND
  Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which play a role in IP maintenance, it may modulate human HF-IP and thus be therapeutically relevant for AA.
  
  
  OBJECTIVE
  To answer the following questions: Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs?
  
  
  METHODS
  Firstly, VIP and VIP receptor (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferon-γ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry.
  
  
  RESULTS
  Here we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level. Furthermore, VIP receptor protein expression, but not VIP(+) nerve fibres, is significantly downregulated in lesional hair bulbs of patients with AA, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed.
  
  
  CONCLUSIONS
  These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in patients with AA, and that VIP is a promising candidate 'HF-IP guardian' that may be therapeutically exploited to inhibit the progression of AA lesions.
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany. marta.bertolini@ukmuenster.de.
authors.forename: M
authors.initials: M
authors.lastname: Bertolini
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pretzlaff
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sulk
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bähr
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gherardini
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Reibelt
authors.affiliation: Department of Ophthalmology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Kinori
authors.affiliation: Department of Internal Medicine and Medical Specialties, University 'La Sapienza', Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.affiliation: DE-MTA 'Lendület' Cellular Physiology Research Group, Departments of Immunology and Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Bíró
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.|Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Paus
mesh_terms: D000506:Alopecia Areata / Q000276:immunology*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018859:Hair Follicle / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000378:metabolism; D012535:Scalp / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D007371:Interferon-gamma