Reduced Inflammatory Threshold Indicates Skin Barrier Defect in Transglutaminase 3 Knockout Mice

被引:34
作者
Bognar, Peter [1 ]
Nemeth, Ilona [1 ]
Mayer, Balazs [1 ]
Haluszka, Dora [1 ]
Wikonkal, Norbert [1 ]
Ostorhazi, Eszter [1 ]
John, Susan [2 ,3 ]
Paulsson, Mats [2 ,3 ]
Smyth, Neil [4 ]
Pasztoi, Maria [5 ]
Buzas, Edit I. [5 ]
Szipocs, Robert [6 ]
Kolonics, Attila [6 ]
Temesvari, Erzsebet [1 ]
Karpati, Sarolta [1 ]
机构
[1] Semmelweis Univ, Dept Dermatol Venereol & Dermatooncol, H-1085 Budapest, Hungary
[2] Univ Cologne, Ctr Biochem, Fac Med, Ctr Mol Med, D-50931 Cologne, Germany
[3] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany
[4] Univ Southampton, Ctr Biosci, Southampton, Hants, England
[5] Semmelweis Univ, Dept Genet Cell & Immune Biol, H-1085 Budapest, Hungary
[6] Wigner RCP, Inst Solid State Phys & Opt, Budapest, Hungary
关键词
FLUORESCEIN-ISOTHIOCYANATE; CONTACT HYPERSENSITIVITY; SENSITIZATION PHASE; KERATINOCYTE TRANSGLUTAMINASE; LAMELLAR ICHTHYOSIS; ATOPIC-DERMATITIS; MICROSCOPY; MUTATIONS; CELLS; TGASE-3;
D O I
10.1038/jid.2013.307
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:105 / 111
页数:7
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