Increased circulating levels of neurotrophins and elevated expression of their high-affinity receptors on skin and gut mast cells in mastocytosis

Abstract

Key Points• Patients with mastocytosis feature increased NT serum levels and elevated expression of modified NT receptors on skin and gut MCs.• NTs might contribute to mastocytosis via increased migration of MC progenitors, MC differentiation, proliferation, and/or survival.

Activation of TRKB receptor in murine hematopoietic stem/progenitor cells induced mastocytosis

“…9 In summary, we provide the first direct evidence for induction of mastocytosis by activation of TRKB in hematopoietic stem/ progenitor cells in vivo. Our data strongly support the findings by Peng et al 1 and their hypothesis and indicate an important role of TRKB in the pathogenesis of mastocytosis.…”

The role and relevance of mast cells in urticaria

“…Human skin mast cells express the G‐protein coupled receptor (GPCR) mas‐related gene X2 (MrgX2) that allows them to be activated for degranulation by polybasic substances, such as compound 48/80 and poly‐L‐lysine . Mast cells also express neuropeptide receptors, such as neurokinin 1 and 2 receptors (NK1R and NK2R), calcitonin gene‐related peptide receptor (CGRPR), and the neurotrophin receptors, tropomyosin‐related kinase A (TrkA), TrkB, and TrkC . Neuropeptides such as substance P, vasoactive intestinal peptide (VIP), and somatostatin, but not eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene‐related peptide (CGRP) stimulate both mast cell degranulation and cytokine production .…”

“…[12][13][14] Mast cells also express neuropeptide receptors, such as neurokinin 1 and 2 receptors (NK1R and NK2R), calcitonin gene-related peptide receptor (CGRPR), and the neurotrophin receptors, tropomyosin-related kinase A (TrkA), TrkB, and TrkC. [15][16][17][18] Neuropeptides such as substance P, vasoactive intestinal peptide (VIP), and somatostatin, but not eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP) stimulate both mast cell degranulation and cytokine production. [19][20][21] Despite the expression of many neuropeptide receptors, the main receptor responsible for mast activation by neuropeptides appears to be MrgX2.…”

Non-IgE mediated mast cell activation

“…They exert biological effects through two types of receptors: p75 and the tropomyosin-related kinase family receptors (Trks). Trks are high affinity receptors for all mature NTs: TrkA for NGF, TrkB for BDNF, TrkC for NT-3, TrkA/TrkB also for NT-3 and NT-4/5 (Peng et al, 2013). Several studies indicate that both murine and human mast cells (HMC-1, hCBMC and human intestinal mast cells) express functional Trks protein, but not p75 (Lorentz et al, 2007;Tam et al, 1997).…”