Mast cell tissue heterogeneity and specificity of immune cell recruitment

Mast cells occupy a unique niche within tissues as long lived perpetrators of IgE mediated hypersensitivity and anaphylaxis, as well as other immune responses. However, mast cells are not identical in different tissues and the impact of this tissue heterogeneity on the interaction with other immune cells and on defined immune responses is still unclear. In this review, we synthesize the characteristics of mast cell heterogeneity in the gut and the skin. Furthermore, we attempt to connect mast cell heterogeneity with functional diversity by exploring differences in mast cell-induced immune cell recruitment in these two model organs. The differential expression of certain receptors on mast cells of different tissues, notably tissue-specific expression patterns of integrins, complement receptors and MRGPRX2, could indicate that tissue environment-dependent factors skew mast cell-immune cell interactions, for example by regulating the expression of these receptors

P2X Receptor-Dependent Modulation of Mast Cell and Glial Cell Activities in Neuroinflammation

From MDPI via Jisc Publications RouterHistory: accepted 2021-08-30, pub-electronic 2021-09-02Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/R505699/1Localisation of mast cells (MCs) at the abluminal side of blood vessels in the brain favours their interaction with glial cells, neurons, and endothelial cells, resulting in the activation of these cells and the release of pro-inflammatory mediators. In turn, stimulation of glial cells, such as microglia, astrocytes, and oligodendrocytes may result in the modulation of MC activities. MCs, microglia, astrocytes, and oligodendrocytes all express P2X receptors (P2XRs) family members that are selectively engaged by ATP. As increased concentrations of extracellular adenosine 5′-triphosphate (ATP) are present in the brain in neuropathological conditions, P2XR activation in MCs and glial cells contributes to the control of their communication and amplification of the inflammatory response. In this review we discuss P2XR-mediated MC activation, its bi-directional effect on microglia, astrocytes and oligodendrocytes and role in neuroinflammation

Experimental validation for chatter stability prediction

This research focused on the experimental validation for chatter stability prediction. An optimum machining was aimed to maximize the material removal rate, whilst maintaining a sufficient stability margin to assure the surface quality. High material removal rate in machining produced self-excited vibration or chatter of the cutting tool and the workpiece. This resulted in a poor surface finish and dimensional accuracy, chipping of the cutter teeth, and also may damage the workpiece as well as machining tool. Frequency response function of a single degree freedom flexural was measured and the cutting stiffness of tools were determined in order to be used in predicting chatter stability using semi discretization method. The aluminium 7075 specimens were used in the milling cutting experiment to validate the chatter stability diagram of mill uniform and variable cutters, where a set of spindle speed and depth of cut had tested. The vibration conditions of machining were identified by analysing the vibration signals and FFT spectrum whether it was stable or in a chatter condition. There are good agreement between predicted stability and cutting experiment for the down-milling operation using uniform 4 flute cutting tool. Stable conditions were shown outside the boundary of chatter region. The optimized cutting tool was predicted to suppress chatter. Machining experiment tests showed there were no chatter vibration conditions during machining process until 1.5 mm depth of cut. According to the results of machining experiment, it was proven that the variable tool had more capability to machining without producing chatter vibration as compared to the regular tool

Bacillus Calmette–Guérin-Induced Human Mast Cell Activation Relies on IL-33 Priming

Bacillus Calmette–Guérin (BCG) vaccine is an attenuated strain of Mycobacterium bovis that provides weak protection against tuberculosis (TB). Mast cells (MCs) are tissue-resident immune cells strategically that serve as the first line of defence against pathogenic threats. In this study, we investigated the response of human MCs (hMCs) to BCG. We found that naïve hMCs exposed to BCG did not secrete cytokines, degranulate, or support the uptake and intracellular growth of bacteria. Since we could show that in hMCs IL-33 promotes the transcription of host-pathogen interaction, cell adhesion and activation genes, we used IL-33 for cell priming. The treatment of hMCs with IL-33, but not IFN-γ, before BCG stimulation increased IL-8, MCP-1 and IL-13 secretion, and induced an enhanced expression of the mycobacteria-binding receptor CD48. These effects were comparable to those caused by the recombinant Mycobacterium tuberculosis (Mtb) 19-KDa lipoprotein. Finally, stimulation of hMCs with IL-33 incremented MC-BCG interactions. Thus, we propose that IL-33 may improve the immunogenicity of BCG vaccine by sensitising hMCs

Human Melanoma-Associated Mast Cells Display a Distinct Transcriptional Signature Characterized by an Upregulation of the Complement Component 3 That Correlates With Poor Prognosis

Cutaneous melanoma is one of the most aggressive human malignancies and shows increasing incidence. Mast cells (MCs), long-lived tissue-resident cells that are particularly abundant in human skin where they regulate both innate and adaptive immunity, are associated with melanoma stroma (MAMCs). Thus, MAMCs could impact melanoma development, progression, and metastasis by secreting proteases, pro-angiogenic factors, and both pro-inflammatory and immuno-inhibitory mediators. To interrogate the as-yet poorly characterized role of human MAMCs, we have purified MCs from melanoma skin biopsies and performed RNA-seq analysis. Here, we demonstrate that MAMCs display a unique transcriptome signature defined by the downregulation of the FcεRI signaling pathway, a distinct expression pattern of proteases and pro-angiogenic factors, and a profound upregulation of complement component C3. Furthermore, in melanoma tissue, we observe a significantly increased number of C3$^{+}$ MCs in stage IV melanoma. Moreover, in patients, C3 expression significantly correlates with the MC-specific marker TPSAB1, and the high expression of both markers is linked with poorer melanoma survival. In vitro, we show that melanoma cell supernatants and tumor microenvironment (TME) mediators such as TGF-β, IL-33, and IL-1β induce some of the changes found in MAMCs and significantly modulate C3 expression and activity in MCs. Taken together, these data suggest that melanoma-secreted cytokines such as TGF-β and IL-1β contribute to the melanoma microenvironment by upregulating C3 expression in MAMCs, thus inducing an MC phenotype switch that negatively impacts melanoma prognosis

Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b

Coronin1a inhibits mast cell degranulation through actin cytoskeletal dynamics while augmenting cytokine secretion, an effect exacerbated by additional loss of Coronin1b

Osteopontin as a new player in mast cell biology

The secreted glycoprotein osteopontin (OPN) sets into motion an astounding variety of activities that range from bone remodeling via immunomodulation to the inhibition of apoptosis. In the current issue of the European Journal of Immunology, OPN now also enters mast cell biology and the regulation of IgE-dependent immune responses since it is reported that connective tissue-type mast cells from fetal murine skin constitutively secrete biologically active OPN. Moreover, it is shown that, in vitro, OPN augments IgE-mediated mast cell degranulation and migration via ligand binding to cognate OPN receptors on the mast cell surface (CD44, alpha v integrin) and that the magnitude of an IgE-mediated passive cutaneous anaphylaxis reaction is augmented by OPN in vivo. Here, we discuss why this newly discovered property of OPN fits well into the emerging concept that OPN may serve as a multi-purpose environmental damage-response protein