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In human MCs, SP, particularly in the presence of interleukin-33 (IL-33), enhances IL-31 gene expression and secretion via MRGPRX2 activation, independent of classical degranulation pathways ( + nociceptive neurons release neuropeptides such as SP which activate MrgprB2 the murine ortholog of human MRGPRX2 on adjacent MCs leading to non-IgE-mediated degranulation and the release of inflammatory mediators including tryptase thereby promoting type 2 inflammation (119)