This is a well-structured study that offers novel insights into the role of MrgprB2 and β-arrestin2 in mast cell-driven neuroimmune interactions during IgE-mediated airway inflammation. The data are robust, and the findings are highly relevant to both basic immunology and potential therapeutic strategies for allergic asthma. That said, a few questions came to mind that I hope the authors might clarify:
1. Since SP is typically derived from nociceptors, it’s intriguing that Tac1 expression was also reduced in MrgprB2−/− mice. Could this suggest a reciprocal signaling loop between mast cells and neurons, possibly mediated by immune-neural feedback?
2. Was there a way to distinguish whether the SP detected after antigen challenge was exclusively neuronal, or might mast cells or other immune cells contribute to its production under these conditions?
3. The upregulation of MrgprB2 in WT mice following sensitization is interesting—do the authors have any insights into what upstream signals may be driving this increase? For example, might IL-4 or IL-13 be involved?
4. The involvement of β-arrestin2 is clearly demonstrated, but was cofilin or any related downstream signaling molecules examined directly in this model?
5. The use of passive IgE sensitization was effective, but how might this approach compare to active sensitization in capturing the complexity of immune priming seen in human asthma?