Abstract
Murine models have highlighted the importance of T-cells and TH2 cytokines in development of allergen-induced airway disease. In contrast, the role of mast cells for the development of allergic airway disease has been controversial. Recent studies in murine models demonstrate a significant contribution of mast cells during the development of airway hyperresponsiveness and airway inflammation. Furthermore these models have allowed identifying certain mast cell-produced mediators (e.g. histamine and leukotriene B4) to be involved in the recruitment of effector T-cells into the lung. Additionally, mast cell-produced TNF can directly activate TH2 cells and contribute to the development of allergic airway disease. These new findings demonstrate a complex role of mast cells and their mediators, not only as effector cells, but also during sensitization and development of allergic airway disease. Therefore mast cells and certain mast cell-produced mediators might be an interesting target for the prevention and treatment of allergic asthma.
Highlights
For decades mast cells have been known as important effector cells for adaptive immune responses
In studies using systemic sensitization with adjuvant hyperresponsiveness (AHR) and airway inflammation are similar in mast cell- or IgE-deficient mice compared to wild-type mice [4,5,6]
Mast cells express several Toll like receptors (TLR) including TLR-4 on their surface and release cytokines and chemokines following exposure to TLR-ligands [14] and mast cell-deficient mice reconstituted with TLR-4 deficient mast cells, did not develop airway eosinophilia following allergen exposure [13]. These findings suggest that IgE-independent mast cell activation through TLR-4 is necessary for sensitization to an allergen administered directly into the lung, further extending the function and role of mast cells in the development of allergic diseases
Summary
For decades mast cells have been known as important effector cells for adaptive immune responses. Murine models have highlighted the importance of T-cells and TH2 cytokines in development of allergen-induced airway disease. Recent studies in murine models demonstrate a significant contribution of mast cells during the development of airway hyperresponsiveness and airway inflammation. Mast cell-produced TNF can directly activate TH2 cells and contribute to the development of allergic airway disease.
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