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KMID : 1225720160080040362
Allergy, Asthma & Immunology Research : AAIR
2016 Volume.8 No. 4 p.362 ~ p.374
House Dust Mite-Derived Chitin Enhances Th2 Cell Response to Inhaled Allergens, Mainly via a TNF-¥á-Dependent Pathway
Choi Jun-Pyo

Lee Sang-Min
Choi Hyun-Il
Kim Min-Hye
Jeon Seong-Gyu
Jang Myoung-Ho
Jee Young-Koo
Yang Sang-hwa
Cho Young-Joo
Kim Yoon-Keun
Abstract
Purpose: Chitin is a potent adjuvant in the development of immune response to inhaled allergens in the airways. According to other studies, chitin is known as multi-faced adjuvants which can induce Th2 responses. Recently, we found that TNF-¥á is a key mediator in the development of Th2 cell response to inhaled allergens. Here, we evaluated the immunologic mechanisms in the development of airway hypersensitivity to inhaled allergens, enhanced by house dust mite (HDM)-derived chitin.

Methods: The role of TNF-¥á and TLRs was evaluated in an airway hypersensitivity mouse model induced by a sensitization with an allergen (ovalbumin, OVA) and HDM-derived chitin using mice with the null mutation of target genes.

Results: The present study showed that airway sensitization with HDM-derived chitin plus OVA enhanced OVA-induced airway inflammation v. OVA alone. This phenotype was associated with the increased expression of Th1, Th2, and Th17 cytokines and also with the enhanced production of OVA-specific IgE, IgG1, and IgG2a. As for T cell responses, OVA-specific Th2 cell response, enhanced by chitin, was abolished by the treatment of chitinase, whereas Th1 and Th17 cell responses enhanced by this treatment. Moreover, the null mutation of the TNF-¥á gene revealed similar effects as the chitinase treatment. In contrast, all the OVA-specific T cell responses, enhanced by chitin, were blocked by the absence of TLR2, but not of TLR1, TLR4, or TLR6.

Conclusions: In conclusion, these data suggest that HDM-derived chitin may enhance airway hypersensitivity to inhaled allergens, via the TLR2-dependent pathway, and that chitin-induced TNF-¥á can be a key mediator in the development of Th2 cell response to inhaled allergens.
KEYWORD
Chitin, house dust mite, Th2 cell response, TNF-¥á
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