J Y Hong1, M Kim1, I S Sol1, K W Kim1, C-M Lee2, J A Elias2, M H Sohn1, C G Lee2,3. 1. Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. 2. Molecular Microbiology and Immunology, Brown University, Providence, RI, USA. 3. Department of Internal Medicine, Hanyang University, Seoul, Korea.
Abstract
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.
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-deficientmice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthmapatients 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.
Authors: Marco van Eijk; Cindy P A A van Roomen; G Herma Renkema; Anton P Bussink; Laura Andrews; Edward F C Blommaart; Alan Sugar; Arthur J Verhoeven; Rolf G Boot; Johannes M F G Aerts Journal: Int Immunol Date: 2005-10-07 Impact factor: 4.823
Authors: Tiffany A Reese; Hong-Erh Liang; Andrew M Tager; Andrew D Luster; Nico Van Rooijen; David Voehringer; Richard M Locksley Journal: Nature Date: 2007-04-22 Impact factor: 49.962
Authors: E Bargagli; C Olivieri; M Margollicci; D Bennett; A Luddi; M Perrone; C Maggiorelli; A Prasse; P Rottoli Journal: Respiration Date: 2010-01-21 Impact factor: 3.580
Authors: Anna J James; Lovisa E Reinius; Marri Verhoek; Anna Gomes; Maciej Kupczyk; Ulf Hammar; Junya Ono; Shoichiro Ohta; Kenji Izuhara; Elisabeth Bel; Juha Kere; Cilla Söderhäll; Barbro Dahlén; Rolf G Boot; Sven-Erik Dahlén Journal: Am J Respir Crit Care Med Date: 2016-01-15 Impact factor: 21.405
Authors: Eun Gyul Kim; Ji Su Leem; Seung Min Baek; Hye Rin Kim; Kyung Won Kim; Mi Na Kim; Myung Hyun Sohn Journal: Allergy Asthma Immunol Res Date: 2022-07 Impact factor: 5.096
Authors: Chang-Min Lee; Chuan-Hua He; Jin Wook Park; Jae Hyun Lee; Suchita Kamle; Bing Ma; Bedia Akosman; Roberto Cotez; Emily Chen; Yang Zhou; Erica L Herzog; Changwan Ryu; Xueyan Peng; Ivan O Rosas; Sergio Poli; Carol Feghali Bostwick; Augustine M Choi; Jack A Elias; Chun Geun Lee Journal: Life Sci Alliance Date: 2019-05-13
Authors: Suh-Young Lee; Chang-Min Lee; Bing Ma; Suchitra Kamle; Jack A Elias; Yang Zhou; Chun Geun Lee Journal: Front Pharmacol Date: 2022-03-17 Impact factor: 5.810