Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-β expression and Foxp3+ Treg cells
J. Y. Hong
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorM. Kim
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorI. S. Sol
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorK. W. Kim
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorC.-M. Lee
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
Search for more papers by this authorJ. A. Elias
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
Search for more papers by this authorCorresponding Author
M. H. Sohn
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Chun Geun Lee, Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
Email: [email protected]
and
Myung Hyun Sohn, Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
C. G. Lee
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
Department of Internal Medicine, Hanyang University, Seoul, Korea
Correspondence
Chun Geun Lee, Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
Email: [email protected]
and
Myung Hyun Sohn, Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
Email: [email protected]
Search for more papers by this authorJ. Y. Hong
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorM. Kim
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorI. S. Sol
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorK. W. Kim
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorC.-M. Lee
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
Search for more papers by this authorJ. A. Elias
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
Search for more papers by this authorCorresponding Author
M. H. Sohn
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Chun Geun Lee, Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
Email: [email protected]
and
Myung Hyun Sohn, Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
C. G. Lee
Molecular Microbiology and Immunology, Brown University, Providence, RI, USA
Department of Internal Medicine, Hanyang University, Seoul, Korea
Correspondence
Chun Geun Lee, Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
Email: [email protected]
and
Myung Hyun Sohn, Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea.
Email: [email protected]
Search for more papers by this authorAbstract
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.
Graphical Abstract
CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest.
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