FIG 2.

Upregulation of LL-37, induction of SP and aberrant activation of cutaneous MCs via MRGPRX2 contributes to rosacea. Microbial assault induces excessive release of LL-37 from keratinocytes which activates MCs via MRGPRX2. Activated MCs release mediators to promote neutrophil recruitment, which generate additional LL-37 to cause chronic inflammation and rosacea pathogenesis via further activation of MCs via MRGPRX2. Moreover, stress induces the release of SP from the sensory neurons, which also activates MCs by MRGPRX2, resulting in the release of chemokines and cytokines. Recruitment of inflammatory cells leads to neurogenic inflammation and exacerbation of rosacea.