FosB/ΔFosB activation in mast cells regulates gene expression to modulate allergic inflammation in male mice

Mast cells are innate immune cells that regulate physiological processes by releasing pre-stored and newly synthesized mediators in response to allergens, infection, and other stimuli. Dysregulated mast cell activity can lead to multisystemic pathologies, but the underlying regulatory mechanisms remain poorly understood. We found that FOSB and {Delta}FOSB, transcription factors encoded by the FosB gene, are robustly expressed in mast cells following IgE-antigen stimulation, suggesting a role in modulating stimulus-induced mast cell functions. Using phenotypic, gene binding, and gene expression analyses in wild-type and mast cell-specific FosB knockout male mice, we demonstrate that FOSB/{Delta}FOSB modulates mast cell functions by limiting reactivity to allergen-like stimuli both in vitro and in vivo. These effects seem to be mediated, at least in part, by FOSB/{Delta}FOSB-driven enhanced expression of DUSP4, a dual-specificity phosphatase that attenuates MAPK signaling. These findings highlight FOSB/{Delta}FOSB as critical regulators of mast cell activity and potential targets for therapeutic intervention. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/592755v2_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@190be2corg.highwire.dtl.DTLVardef@1b53f9borg.highwire.dtl.DTLVardef@631997org.highwire.dtl.DTLVardef@250bc7_HPS_FORMAT_FIGEXP M_FIG C_FIG