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Given a recent report that the IL-3 receptor complex includes the ITAM-containing FcRc chain [41], reduced expression of Syk following FceRI stimulation could theoretically ÀíÂÛÉÏbe involved in both the suppression of CD63 upregulation downstream of FceRI stimulation as well as the suppression of IL-3 induced upregulation of CD203c. To our knowledge, Syk dependence of CD203c upregulation downstream of IL-3 stimulation has not been shown, though it has been reported that IL-3 induced IL-13 expression is not sensitive to the Btk inhibitor, PCI-32765 [40] and that IL-3 does not significantly affect Syk phosphorylation [42]. Because IL-3 directly induces CD203c upregulation and because we chose, as is often done, to include it as a priming agent with all stimulants when this study was designed, we cannot now determine whether peanut OIT independently suppresses CD203c upregulation induced by allergen, anti-IgE or fMLP. It must also be noted that it is possible that OIT suppression of CD63 upregulation may be due to an effect on IL-3 signalling that is specific to its priming of the IgE pathway. However, IL-3 primes basophil degranulation induced by multiple secretagogues including anti-IgE, fMLP, C5a and calcium ionophore and, given the differences of the signaling pathways involved, is thought to effect common distal signalling mediators [43]. Based on this, we believe that our data are most consistent with the interpretation that peanut OIT suppresses FceRI signalling |
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