期刊
ALLERGY
卷 73, 期 8, 页码 1686-1699出版社
WILEY
DOI: 10.1111/all.13426
关键词
asthma; chitotriosidase; regulatory T cell; TGF-beta1; Th2 response
资金
- Ministry of Science, ICT & Future Planning [NRF-2017R1A2B2004043]
- National Research Foundation of Korea [2009-0075056, 2016 R1D1A1B03931794]
- National Institute of Health [U01 HL108638, PO1 HL114501, R01 HL115813]
- Korea Health Industry Development Institute [HI17C0104]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL108638, P01HL114501, R01HL115813] Funding Source: NIH RePORTER
BackgroundChitotriosidase (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. MethodsWild-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. ResultsThe 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-1 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--stimulated conversion of CD4(+)CD25(-) naive T cells to CD4(+)Foxp3(+) Treg cells, suggesting Chit1 is required for optimal effect of TGF-1 in Treg cell differentiation. ConclusionChit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF- expression and Foxp3(+) Treg cells.
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