Mast cells as effector cells: a co-stimulating question

Department of Pharmacology & Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
Trends in Immunology (Impact Factor: 10.4). 09/2007; 28(8):360-5. DOI: 10.1016/
Source: PubMed


Mast cells are currently recognized as effector cells in many settings beyond just allergic reactions, including innate immunity, autoimmunity, chronic inflammatory disorders and atherosclerosis. Signaling pathways of the mast cell response have been widely explored in the past but these are still linked with single axes, such as the high affinity IgE receptor FcepsilonRI, presumably an exclusive determinant of the magnitude of the response to allergen. By contrast, the T cell receptor is viewed as a rich complex of stimulatory and co-stimulatory molecules, setting an array of thresholds to ensure a highly regulated response. Recent observations show that mast cells express various classes of co-stimulatory molecules that modulate their function. These molecules might therefore contribute to the outcome of mast cell-associated pathologies, and constitute new therapeutic targets in such diseases.

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    • "Accordingly, MC effector function plasticity might depend not only on the activatory/inhibitory signals and on the specific released mediators, but also on the secondary, co-stimulatory signals that they receive from their cellular partners in the microenvironment. Thus, MCs specialize in establishing reliable, wideband communication with other cells, orchestrating the overall immune response (Bachelet and Levi-Schaffer, 2007). "
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    ABSTRACT: Mast cells (MCs) are currently recognized as effector cells in many settings of the immune response, including host defense, immune regulation, allergy, chronic inflammation, and autoimmune diseases. MC pleiotropic functions reflect their ability to secrete a wide spectrum of preformed or newly synthesized biologically active products with pro-inflammatory, anti-inflammatory and/or immunosuppressive properties, in response to multiple signals. Moreover, the modulation of MC effector phenotypes relies on the interaction of a wide variety of membrane molecules involved in cell-cell or cell-extracellular-matrix interaction. The delivery of co-stimulatory signals allows MC to specifically communicate with immune cells belonging to both innate and acquired immunity, as well as with non-immune tissue-specific cell types. This article reviews and discusses the evidence that MC membrane-expressed molecules play a central role in regulating MC priming and activation and in the modulation of innate and adaptive immune response not only against host injury, but also in peripheral tolerance and tumor-surveillance or -escape. The complex expression of MC surface molecules may be regarded as a measure of connectivity, with altered patterns of cell-cell interaction representing functionally distinct MC states. We will focalize our attention on roles and functions of recently discovered molecules involved in the cross-talk of MCs with other immune partners.
    Frontiers in Immunology 05/2012; 3:120. DOI:10.3389/fimmu.2012.00120
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    • "In the last decade, the immunological role of mast cells has been steadily expanding. Mast cells regulate other immune cells via the wide variety of cytokines and chemokines secreted upon activation (Galli and Wershil, 1995; Bachelet and Levi-Schaffer, 2007). Additionally , mast cells express receptors that mediate innate immunity, such as toll-like receptors (TLRs; Supajatura et al., 2001; Matsushima et al., 2004), leading to the hypothesis that mast cells can play a significant role in immune responses to infection and other environmental challenges. "
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    ABSTRACT: In addition to their central role in allergy, mast cells are involved in a wide variety of cellular interactions during homeostasis and disease. In this review, we discuss the ability of mast cells to extend their mechanisms for intercellular communication beyond the release of soluble mediators. These include formation of mast cell synapses on antigen presenting surfaces, as well as cell-cell contacts with dendritic cells and T cells. Release of membrane bound exosomes also provide for the transfer of antigen, mast cell proteins, and RNA to other leukocytes. With the recognition of the extended role mast cells have during immune modulation, further investigation of the processes in which mast cells are involved is necessary. This reopens mast cell research to exciting possibilities, demonstrating it to be an immunological frontier.
    Frontiers in Immunology 03/2012; 3:46. DOI:10.3389/fimmu.2012.00046
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    • "They are capable of recognizing, attaching to, phagocytosing, and directly killing a wide variety of opsonized Gram-negative and Gram-positive bacteria [32]. They recognize pathogens through pattern-recognition receptors (Toll-like receptors) and can respond with the induced expression of tumour necrosis factor (TNF)-α, type I interferons, and other inducible cytokines (IL-4, IL-6, IL-8) and chemotactic mediators (CCL3, CCL5, CXCL8) linked to the innate host response [31] [33]. They also contribute to optimal initiation of acquired immunity by orchestrating migration, maturation, and function of dendritic cells and by interacting with T and B cells [34] [35]. "
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    ABSTRACT: Accumulation of mast cells (MCs) in tumours was described by Ehrlich in his doctoral thesis. Since this early account, ample evidence has been provided highlighting participation of MCs to the inflammatory reaction that occurs in many clinical and experimental tumour settings. MCs are bone marrow-derived tissue-homing leukocytes that are endowed with a panoply of releasable mediators and surface receptors. These cells actively take part to innate and acquired immune reactions as well as to a series of fundamental functions such as angiogenesis, tissue repair, and tissue remodelling. The involvement of MCs in tumour development is debated. Although some evidence suggests that MCs can promote tumourigenesis and tumour progression, there are some clinical sets as well as experimental tumour models in which MCs seem to have functions that favour the host. One of the major issues linking MCs to cancer is the ability of these cells to release potent pro-angiogenic factors. This review will focus on the most recent acquisitions about this intriguing field of research. This article is part of a Special Issue entitled: Mast cells in inflammation.
    Biochimica et Biophysica Acta 12/2010; 1822(1):2-8. DOI:10.1016/j.bbadis.2010.11.010 · 4.66 Impact Factor
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