Background: The function of innate receptors including toll like receptor (TLR), conventionally recognized for their antimicrobial effects, has recently been extended to include epithelial barrier regulation. TLR 2 activation was shown to aid tight junction (TJ) repair in atopic dermatitis (AD). However, the role of other TLRs in modulating epidermal barrier in vitro and in vivo remains poorly understood. We investigated the changes of TJ proteins following the activation of TLR 1 and 6 by house dust mite (HDM).
Methods: Firstly, the mRNA levels of TLRs and TJ elements were assayed using real-time RCR in epidermal keratinocytes and a murine model with AD-like lesions activated by HDM allergens. The association between specific TLR activation and the changes of certain TJ proteins was studied in TLR deficient mice.
Results: Both in vitro and in vivo, HDM activated TLR 1 and TLR 6. In addition, HDM induced increased gene expression of TJ proteins including claudin-1, claudin-23 and occludin. These results provide the evidence that HDM triggers the activation of pattern recognition receptors such as TLR 1 and TLR 6 and thus stimulates the modulation of TJ proteins. Moreover, gene expression of TJ proteins including claudin-1, claudin-23 and occludin was not increased in knockout mice of TLR1 (tlr1-/-) and TLR6 (tlr6-/-).
Conclusions: Our data demonstrate that the innate immune activation of the keratinocytes by HDM allergens may lead the preservation of TJ integrity.