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House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling

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Title
House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling
Author(s)
Yong Hyun Jang; Jin Kyeong Choi; Meiling Jin; Young-Ae Choi; Zae Young Ryoo; Hyun-Shik Lee; Pil-Hoon Park; Sun-Uk Kim; Taeg Kyu Kwon; Myoung Ho Jang; Sin-Hyeog Im; Sun Young Moon; Weon Ju Lee; Seok-Jong Lee; Do Won Kim; Sang-Hyun Kim
Publication Date
2017-11
Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY, v.137, no.11, pp.2354 - 2361
Publisher
Elsevier
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-beta activated kinase-1, IkB kinase, and NFkB 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. (c) 2017 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
URI
https://pr.ibs.re.kr/handle/8788114/4194
ISSN
0022-202X
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Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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