| First Author | Paranjape A | Year | 2020 |
| Journal | Cell Immunol | Volume | 356 |
| Pages | 104134 | PubMed ID | 32862025 |
| Mgi Jnum | J:321334 | Mgi Id | MGI:6821166 |
| Doi | 10.1016/j.cellimm.2020.104134 | Citation | Paranjape A, et al. (2020) The Fyn-Stat5 cascade is required for Fcgamma receptor-mediated mast cell function. Cell Immunol 356:104134 |
| abstractText | Mast cells, well established effectors in allergic disease, can be activated by numerous stimuli. We previously found that the Fyn-Stat5B pathway is critical for FcepsilonRI-stimulated mast cell function. Because IgG receptors employ similar signaling pathways, we investigated Fyn-Stat5B function downstream of FcgammaR. We report that FcgammaR elicits Fyn-dependent Stat5B tyrosine phosphorylation in mast cells. As we previously found for Fyn kinase, Stat5B is indispensable for IgG-mediated mast cell cytokine expression and secretion. However, Stat5B KO macrophages responded normally to FcgammaR signaling, indicating a lineage-restricted role for Stat5B. This was consistent in vivo, since passive FcgammaR activation induced anaphylaxis in a macrophage-dominated response even when Stat5B was deleted. We further investigated this lineage restriction using the K/BxN model of inflammatory arthritis. This model exhibits a rapid and transient mast cell-dependent joint inflammation followed days later by a macrophage- and neutrophil-dependent response. Consistent with our hypothesis, Fyn or Stat5B deficiency did not protect mice from late joint swelling, but greatly reduced the early mast cell-dependent response. This was associated with decreased joint and plasma histamine. We conclude that Fyn-Stat5B is a linage-restricted pathway critical for IgG-mediated mast cell responses. |
