Mast Cells in Itch, Pain and Neuro-inflammation
Mast cells are ubiquitously present in most tissues, especially surfaces exposed to the environment, close to blood vessels and nerve fibers, as well as in the meninges and the hypothalamus. Mast cells serve as environmental ‘sensors’ and communicate with hormonal, immune and neural systems leading to immune and inflammatory responses. Mast cells serve as first responders with an inherent ability to rapidly release a plethora of mediators, often selectively, depending on exogenous, or endogenous stimuli. In addition to the classical IgE-dependent mode of stimulation, mast cells react to a multitude of other stimuli, including cytokines, hormones, neuropeptides and neurotransmitters. Different modes of secretion for cytokines/chemokines and classical mediators such as serotonin and histamine suggest possible interplay between the diverse components of the secretory machinery, which is not understood. Nevertheless, strategies to manipulate these different modes of mast cell secretion or to stabilize mast cells offer promising approaches for mast cell-dependent disorders including itch and pain.
Mast cells display heterogeneity in their activity, which depends upon their location and microenvironment. Hence, the mast cell phenotype cannot be generalized and varies depending on location and different pathophysiological conditions, including nociception and degenerative conditions.
New and unexpected functions of mast cells have recently come to light such as their ability to form synapses with dendritic cells and present antigen, as well as mast cell – T cell interactions, especially the ability of the former to increase the numbers of Treg cells playing an anti-inflammatory and immunosuppressive role.
Mast cells have been increasingly involved in conditions involving pain such as fibromyalgia, headache, itch, myalgic encephalomyelitis/chronic fatigue syndrome, sickle cell disease, stroke and traumatic brain injury, thereby attracting greater attention towards their role in pathological conditions.
The aim of this Research Topic is to highlight the current state of knowledge about the involvement of mast cells in critical physiological functions related to the itch, neuroinflammation and pain aiming to identify novel therapeutic targets for multiple disorders.
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Journal of Clinical & Experimental Dermatology Research