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.