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J Invest Dermatol. 2014 Jan;134(1):105-111. doi: 10.1038/jid.2013.307. Epub 2013 Jul 24.

Reduced inflammatory threshold indicates skin barrier defect in transglutaminase 3 knockout mice.

Author information

1
Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary.
2
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.
3
Centre for Biosciences, University of Southampton, Southampton, UK.
4
Department of Genetics, Cell- and Immune Biology, Semmelweis University, Budapest, Hungary.
5
Institute for Solid State Physics and Optics, Wigner RCP, Laser Applications, Budapest, Hungary.
6
Department of Dermatology, Venereology and Dermato-oncology, Semmelweis University, Budapest, Hungary. Electronic address: skarpati@t-online.hu.

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.

PMID:
23884312
DOI:
10.1038/jid.2013.307
[Indexed for MEDLINE]
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