Immunomodulatory mast cells: Negative, as well as positive, regulators of immunity

ArticleinNature Reviews Immunology 8(6):478-86 · July 2008with29 Reads
DOI: 10.1038/nri2327 · Source: PubMed
Mast cells can promote inflammation and other tissue changes in IgE-associated allergic disorders, as well as in certain innate and adaptive immune responses that are thought to be independent of IgE. However, mast cells can also have anti-inflammatory and immunosuppressive functions. Here, we review the evidence that mast cells can have negative, as well as positive, immunomodulatory roles in vivo, and we propose that mast cells can both enhance and later suppress certain features of an immune response.
    • "Upon activation, MCs can produce a broad spectrum of inflammatory cytokines, chemokines, lipid compounds and vasoactive amines, which autoconfer the peculiar capacity to respond to a wide range of external stimuli and drive the immune response (Galli et al., 2008; Gri et al., 2012). The idea that MCs can also translate the immunological effect of AhR activation is extremely new and has been investigated in only 3 papers in the last 2 years. "
    [Show abstract] [Hide abstract] ABSTRACT: The activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact.
    Full-text · Article · Oct 2014
    • "In addition, recent studies have revealed that mast cells are involved in the pathogenesis of autoimmune disease models [3,4]. On the other hand, in some circumstances, mast cells exhibit anti-inflammatory and immunosuppressive functions [24,25], suggesting that mast cells have both positive and negative impacts on immune responses. We found that mast cell-deficient W/Wv mice exhibited reduced susceptibility to CIM as compared with WT mice (Figures 3 and 4) and that the reduced susceptibility of W/Wv mice was restored by the reconstitution of mast cells (Figure 6). "
    [Show abstract] [Hide abstract] ABSTRACT: In addition to the pivotal roles of mast cells in allergic diseases, recent data suggest that mast cells play crucial roles in a variety of autoimmune responses. However, their roles in the pathogenesis of autoimmune skeletal muscle diseases have not been clarified despite their distribution in skeletal muscle. Therefore, the objective of this study is to determine the roles of mast cells in the development of autoimmune skeletal muscle diseases. The number of mast cells in the affected muscle was examined in patients with dermatomyositis (DM) or polymyositis (PM). The susceptibility of mast cell-deficient WBB6F1-KitW/KitWv mice (W/Wv mice) to a murine model of polymyositis, C protein-induced myositis (CIM), was compared with that of wild-type (WT) mice. The effect of mast cell reconstitution with bone marrow-derived mast cells (BMMCs) on the susceptibility of W/Wv mice to CIM was also evaluated. The number of mast cells in the affected muscle increased in patients with PM as compared to patients with DM. W/Wv mice exhibited significantly reduced disease incidence and histological scores of CIM as compared with WT mice. The number of CD8+ T cells and macrophages in the skeletal muscles of CIM decreased in W/Wv mice compared to WT mice. Engraftment of BMMCs restored the incidence and histological scores of CIM in W/Wv mice. Vascular permeability in the skeletal muscle was elevated in WT mice but not in W/Wv mice upon CIM induction. Mast cells are involved in the pathogenesis of inflammatory myopathy.
    Full-text · Article · Mar 2014
    • "Inflammation is a natural host defense response to invading pathogens and tissue injury with the involvement of phagocytic cells such as macrophages, mast cells, dendritic cells, granulocytes and the innate lymphocytes (Galli et al., 2008). In many instances, inflammation is demonstrated to be an important contributor to diseases such as cancer, diabetes and cardiovascular disease. "
    [Show abstract] [Hide abstract] ABSTRACT: The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana. The in silico analysis of inflammatory mediators such as cyclooxygenase (COX) and nuclear factor-kappa B (NF-kB) were performed via molecular docking. Further evaluation of anti-inflammatory effect was conducted in lipopolysaccharide (LPS) induced RAW264.7 macrophages. Suppression of activated NF-kB was analyzed by high content screening. βM triggered inhibition of COX-1 and COX-2 in vitro were studied using biochemical kit. The in vivo model used in this study was carrageenan-induced peritonitis model, where reduction in carrageenan-induced peritonitis is measured by leukocyte migration and vascular permeability. In addition, the evaluation of βM's effect on carrageenan induced TNF-α and IL-1β release on peritoneal fluid was also carried out. Treatment with βM could inhibit the LPS-induced NO production but not the viability of RAW264.7. Similarly, βM inhibited PGE2 production and the cytokines: TNF-α and IL-6. The COX catalysed prostaglandin biosynthesis assay had showed selective COX-2 inhibition with a 53.0±6.01% inhibition at 20µg/ml. Apart from this, βM was capable in repressing translocation of NF-kB into the nucleus. These results were concurrent with molecular docking which revealed COX-2 selectivity and NF-kB inhibition. The in vivo analysis showed that after four hours of peritonitis, βM was unable to reduce vascular permeability, yet could decrease the total leukocyte migration; particularly, neutrophils. Meanwhile, dexamethasone 0.5mg/kg, successfully reduced vascular permeability. The levels of TNF-α and IL-1β in peritoneal fluid was reduced significantly by βM treatment. The current study supports the traditional use of Garcinia mangostana fruit hull for treatment of inflammatory conditions. In addition, it is clear that the anti-inflammatory efficacy of this plant is not limited to the presence of α and ɣ, but β also with significant activity.
    Full-text · Article · Mar 2014
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