Chitotriosidase Regulation of Allergen-Induced Airway Inflammation Airways Hyperresponsiveness and Foxp3+ Treg Cells

Background: The mammalian true chitinases, AMCase and chitotriosidase (CHIT1), are known to be important regulators of inflammation and remodeling. . However, the specific role and mechanism by which CHIT1 regulates Th2 responses has not been defined.

Methods: To define the contribution of CHIT1 during allergic inflammation, wild type (WT) and CHIT1^-/- mice were subjected to OVA or house dust mite (HDM) sensitization and challenge. Bronchoalveolar lavage fluid (BALF) cell number and differential were assessed, chemokines were evaluated using real time-qPCR and enzyme-linked immunosorbent assay (ELISA) and airway hyperresponsiveness (AHR) to metacholine was measured by with a Flexivent apparatus. The proportion of CD4⁺Foxp3⁺ cells and CD4⁺GATA3⁺ cells were determined by flow cytometry.         

 

Results:  In CHIT1^-/- mice, Th2 cytokine production, eosinophil infiltration, IgE production and AHR were increased compared to WT mice. However, the levels of TGF-β and IL-10 expression were significantly decreased in the lungs of CHIT1^-/- mice. Interestingly, the ratio of CD4⁺Foxp3⁺/CD4⁺GATA3⁺cells and their mRNA level were also significantly diminished in CHIT1^-/- mice compared to WT animals. In addition, CHIT1^-/- CD4⁺CD25⁺ Treg cell displayed significantly lower suppression ability in APC–stimulated CD4⁺CD25^- T cells, as compared with WT CD4⁺CD25⁺ Treg cells. These studies demonstrate an ability of CHIT1 to modulate allergen-stimulated Th2 inflammation, AHR and Treg cell number and and function.

 

Conclusion: These results indicate that CHIT1 play a protective effect against allergen-induced allergic airway inflammation and airway responses potentially through the regulation of Foxp3⁺Treg cells.