The role of TLR2 and 4 in Behçet's disease pathogenesis.
TLRs are PRRs that play a pivotal role in sensing exogenous pathogens and endogenous danger signals. Their role in the pathogenesis of inflammatory and immune-related diseases is gradually being unravelled. TLR2 and TLR4 are capable of sensing the oral microbial community, which is considered a potential trigger for Behçet's disease (BD). This study aimed to investigate the expression and function of TLR2 and TLR4 in the oral mucosa of BD. A total of 87 patients was included: 55 BD, 24 healthy controls and eight recurrent aphthous stomatitis. Total RNA was purified from non-lesional oral mucosal brush biopsies and analysed for the presence of TLR2 and TLR4 mRNA, along with their splice variants. The response of peripheral blood mononuclear cells to classical TLR2 and TLR4 agonists was also investigated. TLR2b, TLR2d, TLR2e, TLR4.3 and TLR4.4 were significantly elevated in relapsed BD. A significant defect in the response to cognate agonists of TLR1/2 heterodimer and TLR4 was also observed in BD. The expression of unusual splice variants of TLR2 and TLR4 might explain the observed defect in these receptors' function in BD.
1Centre for Clinical and Diagnostic Oral Sciences. Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Noha
N
Seoudi
Lesley A
LA
Bergmeier
Eleni
E
Hagi-Pavli
David
D
Bibby
Michael A
MA
Curtis
Farida
F
Fortune
D000328:Adult; D017398:Alternative Splicing; D001528:Behcet Syndrome / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology*; D020033:Protein Isoforms / Q000235:genetics; D013281:Stomatitis, Aphthous / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D020033:Protein Isoforms; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
Behçet’s disease; TLR; Toll-like receptors; oral mucosa