title: House Dust Mite-Derived Chitin Enhances Th2 Cell Response to Inhaled Allergens, Mainly via a TNF-α-Dependent Pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine and Medical Center, Seoul, Korea.
authors.forename: Jun Pyo
authors.initials: JP
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Gacheon University College of Medicine, Incheon, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
authors.forename: Hyun Il
authors.initials: HI
authors.lastname: Choi
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine and Medical Center, Seoul, Korea.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Jeon
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Korea.
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
authors.forename: Young Koo
authors.initials: YK
authors.lastname: Jee
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine and Medical Center, Seoul, Korea.
authors.forename: Sanghwa
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine and Medical Center, Seoul, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine and Medical Center, Seoul, Korea. juinea@ewha.ac.kr.
authors.forename: Yoon Keun
authors.initials: YK
authors.lastname: Kim
keywords: Chitin; TNF-α; Th2 cell response; house dust mite