House dust mite-derived chitin enhances Th2 cell response to inhaled allergens, mainly via a TNF-α-dependent pathway

Jun Pyo Choi, Sang Min Lee, Hyun II Choi, Min Hye Kim, Seong Gyu Jeon, Myoung Ho Jang, Young Koo Jee, Sanghwa Yang, Young Joo Cho, Yoon Keun Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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-α 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-α 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-α 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-α can be a key mediator in the development of Th2 cell response to inhaled allergens.

Original languageEnglish
Pages (from-to)362-374
Number of pages13
JournalAllergy, Asthma and Immunology Research
Volume8
Issue number4
DOIs
StatePublished - 2016

Keywords

  • Chitin
  • House dust mite
  • TNF-α
  • Th2 cell response

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