| First Author | Kanagaratham C | Year | 2023 |
| Journal | J Allergy Clin Immunol | Volume | 152 |
| Issue | 2 | Pages | 453-468 |
| PubMed ID | 37030590 | Mgi Jnum | J:338933 |
| Mgi Id | MGI:7485589 | Doi | 10.1016/j.jaci.2023.03.027 |
| Citation | Kanagaratham C, et al. (2023) IgG:FcgammaRIIb signals block effector programs of IgE:FcepsilonRI-activated mast cells but spare survival pathways. J Allergy Clin Immunol |
| abstractText | BACKGROUND: IgE-induced mast cell (MC) degranulation can be inhibited by IgG antibodies, signaling via FcgammaRIIb, but the effects of IgG on IgE-induced MC transcription are unknown. OBJECTIVE: We sought to assess inhibitory IgG:FcgammaRIIb effects on MC responses to IgE using complementary transcriptomic and functional approaches. METHODS: RNA sequencing was performed on bone marrow-derived MCs from wild-type and FcgammaRIIb-deficient mice to identify genes activated following IgE receptor crosslinking that were further modulated in the presence of antigen-specific IgG in an FcgammaRIIb-dependent fashion. Parallel analyses of signaling pathways and allergic responses in vivo were performed to assess the impact of these changes in gene expression. RESULTS: Rapid changes in the transcription of 879 genes occurred in MCs activated by IgE, peaking at 1 hour. Surprisingly, only 12% of these were altered by IgG signaling via FcgammaRIIb, including numerous transcripts involved in orchestrating type 2 responses linked to spleen tyrosine kinase signaling. Consistent with this finding, IgG suppressed IgE-induced phospho-intermediates in the spleen tyrosine kinase signaling pathway. In vivo studies confirmed that the IgG-mediated suppression of both systemic anaphylaxis and MC-driven tissue recruitment of inflammatory cells following allergen challenge was dependent on FcgammaRIIb. In contrast, genes in the STAT5a cell survival pathway were unaltered by IgG, and STAT5a phosphorylation increased after IgE-induced MC activation but was unaffected by IgG. CONCLUSIONS: Our findings indicate that inhibitory IgG:FcgammaRIIb signals block an IgE-induced proallergic program but spare a prosurvival program. |
