The Theranostics Role of Mast Cells in the Pathophysiology of Rosacea

Abstract

Rosacea is a chronic inflammatory cutaneous disorder that adversely affects patient's health and quality of life due to the complex course and the need for repeated treatment. The exact molecular mechanisms of rosacea are unclear. Mast cells are innate immune cells that can be found in virtually all tissues. Recently, increasing evidence has indicated that mast cells have important effects on the pathogenesis of rosacea. In this review article, we describe recent advances of skin mast cells in the development of rosacea. These studies suggested that mast cells can be an important immune cell that connected innate immunity, nerves, and blood vessels in the development of rosacea. Moreover, we review the inhibition of mast cells for the potential treatment of rosacea.

Keywords: dermatology; mast cell; pathophysiology; rosacea; treatment.

Figure 1

The roles of mast cells (MCs) in the pathophysiology of rosacea. In the process of MC activation, triggers (e.g., microbes and UV) can induce the production of LL-37 by keratinocytes. In addition, stress can induce the production of NPs by sensory nerves. LL-37 promotes the activation of MCs through binding to TLR2 on MCs, which can enhance the production of LL-37. LL-37 and NPs can also promote the activation of MCs through MRGPRX2, which promotes the activation of TRPV4 on MCs. After activation, MC degranulation/transgranulation secretes a series of cytokines and mediators, thereby facilitating vasodilation, inflammation, and angiogenesis, which results in neuropathic pain, erythema, telangiectasias, and the formation of papules and pustules. Moreover, MMP9 produced by MCs directly promotes fibrosis, and cytokines and mediators produced by MCs indirectly promote fibrosis through fibroblasts, which secrete FGF. Furthermore, the cross-talk with macrophages, neutrophils, and Th1/Th17 cells may also take part in the pathophysiology of rosacea, which needs further study.