| First Author | Tjota MY | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 5 | Pages | 2287-97 |
| PubMed ID | 23585480 | Mgi Jnum | J:201453 |
| Mgi Id | MGI:5514121 | Doi | 10.1172/JCI63802 |
| Citation | Tjota MY, et al. (2013) IL-33-dependent induction of allergic lung inflammation by FcgammaRIII signaling. J Clin Invest 123(5):2287-97 |
| abstractText | Atopic asthma is a chronic inflammatory disease of the lungs generally marked by excessive Th2 inflammation. The role of allergen-specific IgG in asthma is still controversial; however, a receptor of IgG-immune complexes (IgG-ICs), FcgammaRIII, has been shown to promote Th2 responses through an unknown mechanism. Herein, we demonstrate that allergen-specific IgG-ICs, formed upon reexposure to allergen, promoted Th2 responses in two different models of IC-mediated inflammation that were independent of a preformed T cell memory response. Development of Th2-type airway inflammation was shown to be both FcgammaRIII and TLR4 dependent, and T cells were necessary and sufficient for this process to occur, even in the absence of type 2 innate lymphoid cells. We sought to identify downstream targets of FcgammaRIII signaling that could contribute to this process and demonstrated that bone marrow-derived DCs, alveolar macrophages, and respiratory DCs significantly upregulated IL-33 when activated through FcgammaRIII and TLR4. Importantly, IC-induced Th2 inflammation was dependent on the ST2/IL-33 pathway. Our results suggest that allergen-specific IgG can enhance secondary responses by ligating FcgammaRIII on antigen-presenting cells to augment development of Th2-mediated responses in the lungs via an IL-33-dependent mechanism. |
