title: Reduced inflammatory threshold indicates skin barrier defect in transglutaminase 3 knockout mice.
abstract: Recently, a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development, but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to FITC in TGM3/KO (n=64) and C57BL/6 wild-type (WT) mice (n=36). Cutaneous inflammation was evaluated by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow cytometry from draining lymph nodes. Inflammation-induced significant MEST difference (P<0.0001) was detected between KO and WT mice and was supported also by histopathology. A significant increase of CD4+ CD25+-activated T cells (P<0.01) and elevated serum IgE levels (P<0.05) in KO mice indicated more the development of FITC sensitization than an irritative reaction. Propionibacter acnes-induced intracutaneous inflammation showed no difference (P=0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact cutaneous barrier.
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Bognar
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Ilona
authors.initials: I
authors.lastname: Nemeth
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Mayer
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Dora
authors.initials: D
authors.lastname: Haluszka
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Wikonkal
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Ostorhazi
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: John
authors.affiliation: Center for Biochemistry, Medical Faculty, Center for Molecular Medicine and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.affiliation: Centre for Biosciences, University of Southampton, Southampton, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
authors.affiliation: Department of Genetics, Cell- and Immune Biology, Semmelweis University, Budapest, Hungary.
authors.forename: Maria
authors.initials: M
authors.lastname: Pasztoi
authors.affiliation: Department of Genetics, Cell- and Immune Biology, Semmelweis University, Budapest, Hungary.
authors.forename: Edit I
authors.initials: EI
authors.lastname: Buzas
authors.affiliation: Institute for Solid State Physics and Optics, Wigner RCP, Laser Applications, Budapest, Hungary.
authors.forename: Robert
authors.initials: R
authors.lastname: Szipocs
authors.affiliation: Institute for Solid State Physics and Optics, Wigner RCP, Laser Applications, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Kolonics
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Temesvari
authors.affiliation: Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary. Electronic address: skarpati@t-online.hu.
authors.forename: Sarolta
authors.initials: S
authors.lastname: Karpati
mesh_terms: D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology* / Q000382:microbiology*; D004487:Edema / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000633:toxicity; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011425:Propionibacterium acnes / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
chemical_list: D007073:Immunoglobulin E; C498713:Tgm3 protein, mouse; D011503:Transglutaminases; D016650:Fluorescein-5-isothiocyanate