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Title 

House dust mite increases pro-Th2 cytokines IL-25 and IL-33 via the activation of TLR1/6 signaling

Authors 

Y H JangJ K ChoiM JinY A ChoiZ Y RyooH S LeeP H ParkSun-Uk KimT K KwonM H JangS H ImS Y MoonW J LeeS J LeeD W KimS H Kim

Publisher 

Nature Publishing Group

Issue Date 

2017

Citation 

Journal of Investigative Dermatology

Abstract 

House dust mites have been implicated in the etiology and exacerbation of atopic dermatitis. Diverse factors contribute to house dust mite allergenicity through the activation of innate immunity. We investigated whether Dermatophagoides farinae extract (DFE) allergens mediate innate immune activation through specific toll-like receptors (TLRs) in epidermal keratinocytes, a DFE-induced murine atopic dermatitis model, and human atopic dermatitis lesions. DFE activated the expression of TLR1, TLR6, IL-25, and IL-33 in human primary keratinocytes and HaCaT cells. Knockdown of TLR6 inhibited DFE-induced upregulation of IL-25 or IL-33. In addition, the suppression of TLR1 inhibited the release of IL-33. DFE induced the expression of IL-25 and IL-33 by upregulation of IL-1 receptor-associated kinase 1, transforming growth factor-β activated kinase-1, IκB kinase, and NF-κB pathways. Tlr6?/? mice did not show DFE-induced upregulation of IL-25 and IL-33. Furthermore, DFE-induced upregulation of IL-25 was not induced in Tlr1?/? mice. We also identified upregulated mRNA and protein expression of TLR1, TLR6, IL-25, and IL-33 in human atopic dermatitis skin lesions with high house dust mite sensitization. We found that DFE-induced activation of TLR1 and TLR6 may cause polarization toward a T helper type 2 immune response via the release of IL-25 and IL-33

ISSN 

0022-202X

Link 

http://dx.doi.org/10.1016/j.jid.2017.03.042

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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