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Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3+ Treg cells.

 J. Y. Hong  ;  M. Kim  ;  I. S. Sol  ;  K. W. Kim  ;  C.‐M. Lee  ;  J. A. Elias  ;  M. H. Sohn  ;  C. G. Lee 
 Allergy, Vol.73(8) : 1686-1699, 2018 
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Issue Date
TGF-beta1 ; Th2 response ; asthma ; chitotriosidase ; regulatory T cell
BACKGROUND: Chitotriosidase (chitinase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. However, the role and the mechanisms that underlie these contributions to the diseases have not been defined. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. METHODS: Wild-type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthma patients and compared to control. RESULTS: The levels of sputum Chit1 were significantly increased in the patients with childhood asthma. Mice with Chit1 null mutation demonstrated enhanced allergic Th2 inflammatory and cytokine and IgE responses to OVA or house dust mite allergen sensitization and challenge. However, the expression levels of TGF-β1 were significantly decreased with a diminished number of Foxp3+ regulatory T cells (Treg) in the lungs of Chit1-/- mice compared to WT controls. In vitro, the absence of Chit1 significantly reduced TGF-β-stimulated conversion of CD4+ CD25- naïve T cells to CD4+ Foxp3+ Treg cells, suggesting Chit1 is required for optimal effect of TGF-β1 in Treg cell differentiation. CONCLUSION: Chit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF-β expression and Foxp3+ Treg cells.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
김경원(Kim, Kyung Won) ORCID logo https://orcid.org/0000-0003-4529-6135
김미나(Kim, Mina) ORCID logo https://orcid.org/0000-0002-1675-0688
설인숙(Sol, In Suk) ORCID logo https://orcid.org/0000-0003-2470-9682
손명현(Sohn, Myung Hyun) ORCID logo https://orcid.org/0000-0002-2478-487X
홍정연(Hong, Jung Yeon) ORCID logo https://orcid.org/0000-0003-0406-9956
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