| Asthma and allergy are characterized by dysregulation of inflammatory responses toward Th2 and interestingly, increased serum IgE levels are highly correlated with the severity of the disease. The physiological role of IgE however remains poorly elucidated. We have previously shown lymphotoxin (LT) is required for maintaining physiological levels of serum IgE that minimizes Th1-mediated airway inflammation, suggesting IgE plays a physiological role in regulating T helper cell differentiation. We therefore, sought to determine the mechanism in which IgE maintains this component of inflammation. This study demonstrates LT-/- mice have similar numbers of basophils and mast cells (MC), two cell types known to secrete pre-formed IL-4, the required Th2 cytokine, in response to IgE mediated stimulation but lack surface IgE. Bone marrow derived MC stimulated by IgE are sufficient to skew CD4 + T cells towards Th2 under otherwise Th1 priming conditions. This process is IgE dependent, IL-4 independent and utilizes a soluble factor. Additionally, LT-/- mice have increased levels of IL-12 in the spleen and lung, suggesting IgE dictates the development of Th1 responses in vivo. IgE directly stimulates DC through FcgammaRIII to suppress IL-12 in vitro and influences APC to skew CD4+ T cells toward Th2. Taken together, a duality exists in the mechanism of IgE-mediated T helper cell differentiation in which IgE stimulates basophils or mast cells to promote Th2 differentiation and IgE influences Th1 generation through interaction of DC via FcgammaRIII to inhibit IL-12 production. |
