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Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine.

ABSTRACT: Migraine is a primary headache disorder which has complex neurogenic pathophysiological mechanisms still requiring full elucidation. The sensory nerves and meningeal mast cell couplings in the migraine target tissue are very effective interfaces between the central nervous system and the immune system. These couplings fall into three categories: intimacy, cross-talk and a shared fate. Acting as the immediate call-center of the neuroimmune system, mast cells play fundamental roles in migraine pathophysiology. Considerable evidence shows that neuroinflammation in the meninges is the key element resulting in the sensitization of trigeminal nociceptors. The successive events such as neuropeptide release, vasodilation, plasma protein extravasation, and mast cell degranulation that form the basic characteristics of the inflammation are believed to occur in this persistent pain state. In this regard, mast cells and sensory neurons represent both the target and source of the neuropeptides that play autocrine, paracrine, and neuro-endocrine roles during this inflammatory process. This review intends to contribute to a better understanding of the meningeal mast cell and sensory neuron bi-directional interactions from molecular, cellular, functional points of view. Considering the fact that mast cells play a sine qua non role in expanding the opportunities for targeted new migraine therapies, it is of crucial importance to explore these multi-faceted interactions.

SUBMITTER: Koyuncu Irmak D

PROVIDER: S-EPMC6460506 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine.

Koyuncu Irmak Duygu D Kilinc Erkan E Tore Fatma F

Frontiers in cellular neuroscience 20190405

Migraine is a primary headache disorder which has complex neurogenic pathophysiological mechanisms still requiring full elucidation. The sensory nerves and meningeal mast cell couplings in the migraine target tissue are very effective interfaces between the central nervous system and the immune system. These couplings fall into three categories: intimacy, cross-talk and a shared fate. Acting as the immediate call-center of the neuroimmune system, mast cells play fundamental roles in migraine pat ...[more]

PMID: 31024263

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Project description:Neuroimmune interactions are important in the pathophysiology of many chronic inflammatory diseases, particularly those associated with alterations in sensory processing and pain. Mast cells and sensory neuron nerve endings are found in areas of the body exposed to the external environment, both are specialized to sense potential damage by injury or pathogens and signal to the immune system and nervous system, respectively, to elicit protective responses. Cell adhesion molecule 1 (CADM1), also known as SynCAM1, has previously been identified as an adhesion molecule which may couple mast cells to sensory neurons however, whether this molecule exerts a functional as well as structural role in neuroimmune cross-talk is unknown. Here we show, using a newly developed in vitro co-culture system consisting of murine bone marrow derived mast cells (BMMC) and adult sensory neurons isolated from dorsal root ganglions (DRG), that CADM1 is expressed in mast cells and adult sensory neurons and mediates strong adhesion between the two cell types. Non-neuronal cells in the DRG cultures did not express CADM1, and mast cells did not adhere to them. The interaction of BMMCs with sensory neurons was found to induce mast cell degranulation and IL-6 secretion and to enhance responses to antigen stimulation and activation of Fc?RI receptors. Secretion of TNF? in contrast was not affected, nor was secretion evoked by compound 48/80. Co-cultures of BMMCs with HEK 293 cells, which also express CADM1, while also leading to adhesion did not replicate the effects of sensory neurons on mast cells, indicative of a neuron-specific interaction. Application of a CADM1 blocking peptide or knockdown of CADM1 in BMMCs significantly decreased BMMC attachment to sensory neurites and abolished the enhanced secretory responses of mast cells. In conclusion, CADM1 is necessary and sufficient to drive mast cell-sensory neuron adhesion and promote the development of a microenvironment in which neurons enhance mast cell responsiveness to antigen, this interaction could explain why the incidence of painful neuroinflammatory disorders such as irritable bowel syndrome (IBS) are increased in atopic patients.

Dataset Information

Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine.

Publications

Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine.

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