Soluble Transforming Growth Factor Beta-1 enhances murine mast cell cytokine release

Abstract

Abstract TGF-β1 is traditionally known as an immunosuppressive cytokine. Previous studies have investigated its effects on FcɛRI-dependent mast cell activation, yet there is an incomplete understanding of TGF-β1 on mast cell function, for example, without sensitization to IgE. We investigated the effects of soluble TGF-β1 on IL-6 and IL-13 cytokine production in C57BL/6 bone marrow-derived mast cells in the presence and absence of FcɛRI-mediated activation. Our experiments found IL-6 production to be significantly enhanced independent of IgE sensitization or FcɛRI crosslinking; this was similar to treatment with stem cell factor (SCF), which also enhanced IL-6 production in this resting state. Additionally, IL-13 production was significantly enhanced following IgE-mediated stimulation of TGF-β1 treated mast cells; an effect independent of IgE was not observed, and treatment with SCF had no significant impact. Lastly, via confocal microscopy, we interrogated the cell-surface expression of FcɛRI, CD117 (c-Kit; SCF receptor), and TGFβRII with and without soluble TGF-β1 and/or FcɛRI crosslinking. This experiment revealed no apparent effect of TGF-β1 on FcɛRI and CD117 receptor co-localization – in both treatments we observed an equivalent decline in co-localization following IgE-mediated activation. TGFβRII was also found to weakly co-localize with those receptors, however this co-localization was unchanged across all treatments. Together, our findings provide novel insight into the stimulatory role of TGF-β1 on mast cell function both in the presence and absence of an allergic-like stimulus, suggesting alternative pathways play a pivotal role in regulating mast cell function beyond that of a canonical IgE-mediated pathway.