Role of mast cells and basophils in pruritus

Abstract

To protect our body systems, there is a constant interactive conversation between the skin nervous and immune system. Important elements of this conversation in the skin include mast cells, basophils, and sensory nerve fibers. These cells employ a vast array of sensors that detect danger and react accordingly. This reaction, summarized as neurogenic inflammation, manifests at the conscious level as sensations including pain and itch. Here we provide a perspective on the blossoming knowledge that is illuminating connections between mast cells, basophils, and sensory nerve fibers in the mediation of itch. We discuss established mediators and receptors, in particular cytokine and neuropeptide pathways, upstream proteases, and proteinase-activated receptors, and the emerging role of mas-related G-protein-coupled receptors in itch.

Neuro-immune crosstalk and allergic inflammation

“…Sensory nervederived substance P induces mast cell degranulation and release of histamine, TNF-α, leukotriene B 4 , and vascular endothelial growth factor (VEGF) (ref. 33 and Figure 2). VEGF further promotes endothelial cell proliferation and vascularization, facilitating the inflammatory process.…”

Neuroimmune interactions in chronic itch of atopic dermatitis

“…4,34,35 Some AD-associated cytokines, IL-31 and thymic stromal lymphopoietin (TSLP), can directly promote itch via activation of pruritoceptive TRPV1+ TRPA1+ neurons that express their receptors. 4,34,35 Some AD-associated cytokines, IL-31 and thymic stromal lymphopoietin (TSLP), can directly promote itch via activation of pruritoceptive TRPV1+ TRPA1+ neurons that express their receptors.…”

“…Immune cell-derived factors T helper cell 2 (Th2) lymphocytes, eosinophils, neutrophils and mast cells amplify inflammatory and pruritoceptive pathways in AD by releasing cytokines and neurogenic peptides. 4,34,35 Some AD-associated cytokines, IL-31 and thymic stromal lymphopoietin (TSLP), can directly promote itch via activation of pruritoceptive TRPV1+ TRPA1+ neurons that express their receptors. 36,37 In addition, IL-4 may potentiate itch by sensitizing itch-sensory neurons to direct pruritogens, such as histamine and IL-31.…”

What we know (and don't know) about the biology and functions of mast cells and basophils

“…In addition, they outline our current gaps in knowledge, unmet needs and unanswered questions. Steinhoff and co‐workers discuss the role of mast cells and basophils in itch . Their focus is on underlying mechanisms, mediators and receptors, especially on proteinase‐activated receptors (PARs) and mas‐related G protein‐coupled receptors (Mrgprs).…”

“…Surprisingly, the role and relevance of mast cells in urticaria has not been reviewed and critically discussed during the last twenty years.Church et al 13 have taken on the task to put together the various independent lines of evidence that support the central role of mast cells in urticaria, primarily chronic urticaria. In addition, they outline our current gaps in knowledge, unmet needs and unanswered questions.Steinhoff and co-workers discuss the role of mast cells and basophils in itch 14. Their focus is on underlying mechanisms, mediators and receptors, especially on proteinase-activated receptors (PARs) and masrelated G protein-coupled receptors (Mrgprs).…”