Mast cells within cellular networks

Abstract

Mast cells are highly versatile in terms of their mode of activation by a host of stimuli and their ability to flexibly release a plethora of biologically highly active mediators. Within the immune system, mast cells can best be designated as an active nexus interlinking innate and adaptive immunity. Here we try to draw an arc from initiation of acute inflammatory reactions to microbial pathogens to development of adaptive immunity and allergies. This multifaceted nature of mast cells is made possible by interaction with multiple cell types of immunologic and nonimmunologic origin. Examples for the former include neutrophils, eosinophils, T cells, and professional antigenpresenting cells. These interactions allow mast cells to orchestrate inflammatory innate reactions and complex adaptive immunity, including the pathogenesis of allergies. Important partners of nonimmunologic origin include cells of the sensory neuronal system. The intimate association between mast cells and sensory nerve fibers allows bidirectional communication, leading to neurogenic inflammation. Evidence is accumulating that this mast cell/nerve crosstalk is of pathophysiologic relevance in patients with allergic diseases, such as asthma.

The Theranostics Role of Mast Cells in the Pathophysiology of Rosacea

“…Transcriptome analysis on facial biopsies of rosacea patients revealed significant upregulation of macrophages, neutrophils, mast cells, and T helper 1 cell/T helper 17 cell (Th1/Th17)polarized immune cells (52). Although there are no reports on the interaction between MCs and other immune cells, including macrophages, neutrophils, and T cells in rosacea, many studies have proven that MCs can be activated by other immune cells or can activate neighboring cells through the release of inflammatory mediators (19,53). Macrophage is an antigen-presenting cell (APC) that is regarded as a significant orchestrator of skin immunity.…”

Mast Cell Functions Linking Innate Sensing to Adaptive Immunity

“…d.) injection of MC granules into MC-deficient mice was sufficient to induce a profound expansion of T cells indicating their adjuvant effect.Extending the finding of Kunder et al[65], we provided evidence that MC degranulation in the periphery may exert long-distance effects on LN-borne adaptive T cell responses in two ways:(a) trafficking of MC granules via lymphatic vessels towards the DLNs, and (b) active shuttling of MC granules by DCs along with DC modulating effects[64].Beside MC granules, MC-derived exosomes offer an additional mechanism for intercellular communication, by having greater stability in the interstitial space compared to soluble mediators[69,84] and being able to promote DC maturation and antigen-presenting capacity[85,86].Confirming our findings in CHS, Otsuka et al showed impaired skin DC maturation and migration in the absence of MCs and the relevance of a direct interaction between DCs and MCs, leading to an upregulation of membrane-bound TNF by MCs [87]. Given the close proximity of MCs and DCs in peripheral tissues, especially in the skin, a physical cell-to-cellinteraction was considered likely and studied in several in vitro studies.…”

CD16highCD62Ldim neutrophils induce nerve‐mediated airway hyperreactivity

“…Eosinophils have recently been shown to increase airway sensory nerve density and hyperresponsiveness 12 . In analogy, mast cells have been demonstrated to interact with sensory nerves, by releasing inflammatory mediators as well by direct cell‐cell‐mediated interaction via synaptic cell adhesion molecules 13 . The present study was designed to investigate if the newly identified subsets of neutrophils also could interfere with airway sensory nerve activity, causing nerve‐mediated airway obstruction and hyperresponsiveness.…”