Neuroendocrinology of mast cells: Challenges and controversies

215

198

This review presents evidence that the skin mast cell, in particular the MC subtype, is the primary effector cell in urticaria. Mast cells are located in the upper dermis, the ideal situation for wheal formation and sensory nerve stimulation. Increased numbers of mast cells are found in both lesional and non-lesional skin in CSU and inducible urticaria. Mast cell degranulation in the area of wheals has been demonstrated repeatedly by light and electron microscopy. Histamine, PGD and tryptase are found in the venous blood draining wheal formation. The last 2 are specific for mast cells rather than basophils. Mast cell reactivity is increased in active urticaria by local inflammatory cytokines and neuropeptides. Mast cell cytokines and neuropeptides, particularly nerve growth factor, induce a Th2 type inflammation that is particularly obvious at the sites of whealing. In conclusion, autoimmunity, either of Type 1 viz. IgE antibodies to local autoallergens, or Type 2b, viz. IgG autoantibodies to IgE or its receptor, are considered to be the most frequent causes of CSU. In both cases, the mast cell is likely to be the axial cell in producing the wheals.

Section: Is Mast Cell Reactivity Changed?mentioning

confidence: 99%

The role and relevance of mast cells in urticaria

Church

Kolkhir

Metz

et al. 2018

215

198

“…Several other processes have been recognized including tunneling nanotubes (TNT), physical extension via pseudopodia‐like structures, and extracellular trap formation, which may allow for increased interaction of mast cells with vasculature, nervous system, and immune cells, described in detail below. Therefore, mast cells exhibit extraordinary complexity and contribute to diverse functions . This review will examine the interactions of mast cells with the central and peripheral neural systems, pathophysiological mechanisms, and therapeutic targets to treat pain and pruritus.…”

Section: Mast Cells As a “Power House”mentioning

confidence: 99%

Mast cell‐neural interactions contribute to pain and itch

Gupta

Harvima

2018

206

189

Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a "power house" by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer.

“…MRG GPCR activation may also be useful in vaccination strategies providing an adjuvant effect . Given its reactivity with neuropeptides such as SP and VIP, the receptor represents also a component of the communication between the neuronal and immune system participating, for example, in neurogenic inflammation responsible for pain and itch in agreement with their localization close to nerve endings that release these peptides. Taken together, the description of this new receptor explains to a large extent the extraordinary capacity of MCs to respond to a diverse array of compounds of different origin that have the characteristics of being charged positively.…”

Section: G‐protein‐coupled Receptors (Gpcrs)mentioning

confidence: 99%

“…Several chronic inflammatory skin disorders such as psoriasis, atopic dermatitis can worsen with stress. As NT serum levels are elevated in these diseases, they may contribute to the aggravation of symptoms . Conversely, MCs can also reduce NT toxicity in septic peritonitis induced by cecum ligation and puncture reducing NT levels and NT‐induced hypotension .…”

Section: G‐protein‐coupled Receptors (Gpcrs)mentioning

confidence: 99%

Non‐IgE mediated mast cell activation

Redegeld

Kumari

et al. 2018

154

105

Mast cells (MCs) are innate immune cells that are scattered in tissues throughout the organism being particularly abundant at sites exposed to the environment such as the skin and mucosal surfaces. Generally known for their role in IgE-mediated allergies, they have also important functions in the maintenance of tissue integrity by constantly sensing their microenvironment for signals by inflammatory triggers that can comprise infectious agents, toxins, hormones, alarmins, metabolic states, etc. When triggered their main function is to release a whole set of inflammatory mediators, cytokines, chemokines, and lipid products. This allows them to organize the ensuing innate immune and inflammatory response in tight coordination with resident tissue cells, other rapidly recruited immune effector cells as well as the endocrine and exocrine systems of the body. To complete these tasks, MCs are endowed with a large repertoire of receptors allowing them to respond to multiple stimuli or directly interact with other cells. Here we review some of the receptors expressed on MCs (ie, receptors for Immunoglobulins, pattern recognition receptors, nuclear receptors, receptors for alarmins, and a variety of other receptors) and discuss their functional implication in the immune and inflammatory response focusing on non-IgE-mediated activation mechanisms.