의과대학/박사The mammalian true chitinase, Acidic mammalian chitinase (AMCase) and chitotriosidase (Chitnase 1, Chit1), were known to be important regulators of inflammation and remodeling. Allergic asthma is the immunologic hypersensitive disease which is characterized by eosinophil recruitment, increase of mucus secretion and airway hyperresponsiveness. During asthma development, Th2 cells modulate pathological symptoms of asthma by secretion of IL-4, IL-5 and IL-13. However, the specific role and mechanism by which Chit1 regulates Th2 responses has not been fully defined.
To explore the contribution of Chit1 during allergic inflammation, wild type (WT) and chitotriosidase deficiency (Chit1-/-) mice were subjected to ovalbumin (OVA) or house dust mite (HDM) sensitization and challenge. Bronchoalveolar lavage fluid (BALF) cell number and differential were assessed, cytokines and total and OVA-specific IgE were evaluated using 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.
In OVA-challenged Chit1-/- mice, Th2 cytokine production, eosinophil infiltration, IgE production and AHR were increased compared to WT mice. The levels of TGF-β1 and IL-10 expression were also significantly decreased in the lungs of Chit1-/- mice. The ratio of CD4+Foxp3+/CD4+GATA3+cells and their mRNA level were significantly diminished in Chit1-/- mice compared to WT mice. In naïve mice, the percentage and proliferation of Treg cells were comparable to WT cells. In vitro studies, Chit1-/- CD4+CD25-T cells upregulated Foxp3 and TGF-β receptors following TGF-β1 and rChit1 stimulation as much as WT CD4+CD25- T cells. In addition, Chit1-/- CD4+CD25+ Treg cell displayed similar suppression ability in APC-stimulated CD4+CD25- T cells, as compared with WT CD4+CD25+ Treg cells.
Collectively, 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.ope
