Interaction of peripheral nerves and mast cells, eosinophils, and basophils in the development of pruritus

Abstract

Mast cells, eosinophils and basophils are central effector immune cells in allergic skin inflammation including atopic dermatitis (AD). Recent studies revealed that the bidirectional interaction between these three immune cell types (mast cells, eosinophils and basophils) and the nervous system is involved in the pathogenesis of neurogenic inflammation, pain and pruritus. Emerging evidence shows that these cells are the main source of pruritogens such as histamine, neuropeptides and cytokines, which are potential new therapeutic targets for drug development in chronic pruritus. For instance, many Th2 cytokines including interleukin (IL)‐4, 13 and 31 have been recognized as some of the most promising targets for the treatment of chronic pruritus in AD. In this review, we highlight the link between these three immune cell subsets and peripheral nerves, with emphasis on the development of chronic pruritus such as AD. We present cytokines and receptors of these three immune cells and peripheral nerves, and discuss the therapeutic potential of targeting these neuro‐immunological processes.

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells

“…[20][21][22][23][24][25] In addition, there is emerging evidence suggesting that MCs may potentially be involved in conditions associated with neurogenic inflammation, as exemplified by a proposed role for MCs in mediating inflammation, pain, and tissue healing. 6,[26][27][28] In support of functional MC-nerve communication, MCs are frequently found in close association with nerve endings. [26][27][28] However, the mechanisms by which MCs may interact with peripheral nerves have been mostly elusive.…”

“…6,[26][27][28] In support of functional MC-nerve communication, MCs are frequently found in close association with nerve endings. [26][27][28] However, the mechanisms by which MCs may interact with peripheral nerves have been mostly elusive. One scenario is that secretory products released from MCs can interact with nerve Fig.…”

Do Mast Cells Have a Role in Tendon Healing and Inflammation?

“…Most notably, mast cells are strongly implicated in allergic disorders but there is also evidence supporting the contribution of mast cells in various autoimmune diseases, fibrosis, cancer, skin inflammation, and metabolic disorders [48,[60][61][62][63][64][65][66][67]. In addition, there is emerging evidence suggesting that mast cells potentially could be involved in conditions associated with neurogenic inflammation [51,[68][69][70][71]. In support of a functional nerve:mast cell communication, mast cells are frequently found in close association with nerve endings [69][70][71].…”

“…In addition, there is emerging evidence suggesting that mast cells potentially could be involved in conditions associated with neurogenic inflammation [51,[68][69][70][71]. In support of a functional nerve:mast cell communication, mast cells are frequently found in close association with nerve endings [69][70][71]. However, the mechanisms by which mast cells could respond to nerve signaling have been mostly elusive.…”

Switch to Itch—The many novel facets of pruritus research

“…Hashimoto and colleagues (Miami, USA) covered the neglected but fascinating role of basophils in chronic itch and pruritic skin diseases, as well as the topographical differences of C nerve fibres and their implication in itch induction . Nakashima and colleagues (Kyoto, Japan) presented current knowledge on the interactions and communication of peripheral nerves and three immune cell subsets, mast cells, eosinophils and basophils, while Campion (Dublin, Ireland) and colleagues demonstrated novel data on IL4 and IL13 and their role as pruritogens when injected intradermally. Talagas et al (Brest, France) added their understanding of the crosstalk between keratinocytes and skin nerves; colleagues from the same centre, Huet and Misery, shed light on the mechanisms behind sensitive skin a common itchy problem when using cosmetics and toiletries namely that the epidermis represents a huge polymodal nociceptor.…”