Trends in Neurosciences
ReviewMast Cells in Neuroimmune Interactions
Section snippets
The Mast Cell: A Neuroimmune Archetype
The nervous and immune systems play critical roles in regulating processes required for maintaining physiological homeostasis, responding to acute stressors, and protecting against external threats. The functions of these two adaptive systems are often considered independently as evidenced by the distinct scientific disciplines of neuroscience and immunology. However, in reality, homeostasis and host defense require orchestrated responses involving constant communication between nervous and
An Overview of Mast Cells
Mast cells are long-lived tissue resident cells of hematopoietic origin (i.e., they derive from hematopoietic stem cells, which give rise to blood cells). While most recognized as the major effector cells of immunoglobulin E (IgE)-mediated allergic inflammation, mast cells play important roles in diverse physiological and pathological processes.
From an evolutionary perspective, cells with mast cell-like characteristics predate the emergence of the chordates >500 million years ago [8]. However,
Anatomical Relationships between Mast Cells and Neurons
The close spatial relationship between mast cells and peripheral myelinated and unmyelinated nerves has been known for over 30 years and has been identified in essentially every tissue examined 33, 34. Mast cells are found in particularly high numbers in tissues innervated by small caliber sensory A-delta and C-fibers responsible for pain transmission, and these anatomic associations between mast cells and nerves are even more evident at sites of inflammation 35, 36.
While studies suggest that
Mast Cell Modulation of Neural Function
The somatosensory system is a prime example of the mast cell–nerve functional unit in action. Mast cells are important first responders in protective pain responses that provoke withdrawal from noxious environmental stimuli. The activation of mast cells, in response to immunologic, chemical, or physical stimuli and the consequent release of molecules that actuate/sensitize nociceptors directly contributes to pain sensation [43]. In allergic inflammation, it is proposed that IgE-mediated mast
Neural Regulation of Mast Cells
Mast cells express receptors for a range of neurotransmitters, and consequently can be modulated by them. These neurotransmitters include: classical neurotransmitters such as acetylcholine [58]; neuropeptides such as substance P, CGRP, vasoactive intestinal peptide, and neurotensin [59]; and the gaseous neurotransmitters nitric oxide and hydrogen sulfide 60, 61 (Figure 2). The effects of these diverse neurotransmitters on mast cell function vary from direct activation to enhancement or
Mast Cells and the Brain
Mast cell–nerve interactions are not restricted to the periphery, as mast cells are also present, albeit in lower overall numbers, in the brain [82]. The combination of mast cell plasticity and the unique environment of the central nervous system leads to a very distinct brain mast cell phenotype. For example, under normal conditions brain parenchymal mast cells lack expression of both the high affinity IgE receptor, FcεRI [83], and receptors for the major mast cell survival factor, SCF [84],
Concluding Remarks
The functional relationship between mast cells and nerves can be seen as an archetype of neuroimmune communication. Nerve-mast cell interactions regulate, or are suggested to regulate, a plethora of physiological and pathophysiological responses (Figure 3). However, while interactions between mast cells and all branches of the nervous system have been documented for decades, the full extent to which such interactions influence health and disease is still obscure (see Outstanding Questions).
Acknowledgements
This work was funded by grants from the Office of Naval Research (N00014-14-1-0787) and the Natural Sciences and Engineering Research Council of Canada.
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