We have previously demonstrated the immunosuppressive effects of TGFβ1 on IgE signaling in human and mouse mast cells in vitro. Here we extend our focus to in vivo models, including mast cell-dependent airway inflammation. TGFβ1 injection into unimmunized mice reduced peritoneal mast cell numbers and their expression of the high affinity IgE receptor, as well as cKit. Further, TGFβ1 delivered as an aerosol to ovalbumin-immunized mice decreased pulmonary eosinophilic inflammation and mucus production. TGFβ1 did not affect Syk, Stat5, Fyn or Akt mRNA expression. However, mast cell Fyn and Stat5 protein levels were diminished by TGFβ1 treatment in vitro, while Akt and Syk were unaffected. Interestingly, we found that mast cells from the 129/SvJ mouse strain were resistant to TGFβ1-mediated suppression. Unlike their C57BL/6 counterparts, 129/SvJ mast cells did not demonstrate reduced IgE receptor expression or IgE-mediated cytokine production after culture with TGFβ1. These data show that TGFβ1 is a potent suppressor of the mast cell response that may be altered by host genetic makeup. We further find that the effects of TGFβ1 include selective reduction in key IgE-mediated signaling molecules.
- Copyright © 2011 by The American Association of Immunologists, Inc.