Summary
Mast cells are hematopoietic cells that reside in virtually all vascularized tissues and that represent potential sources of a wide variety of biologically active secreted products, including ...diverse cytokines and growth factors. There is strong evidence for important non‐redundant roles of mast cells in many types of innate or adaptive immune responses, including making important contributions to immediate and chronic IgE‐associated allergic disorders and enhancing host resistance to certain venoms and parasites. However, mast cells have been proposed to influence many other biological processes, including responses to bacteria and virus, angiogenesis, wound healing, fibrosis, autoimmune and metabolic disorders, and cancer. The potential functions of mast cells in many of these settings is thought to reflect their ability to secrete, upon appropriate activation by a range of immune or non‐immune stimuli, a broad spectrum of cytokines (including many chemokines) and growth factors, with potential autocrine, paracrine, local, and systemic effects. In this review, we summarize the evidence indicating which cytokines and growth factors can be produced by various populations of rodent and human mast cells in response to particular immune or non‐immune stimuli, and comment on the proven or potential roles of such mast cell products in health and disease.
Immunoglobulin E (IgE) antibodies and mast cells have been so convincingly linked to the pathophysiology of anaphylaxis and other acute allergic reactions that it can be difficult to think of them in ...other contexts. However, a large body of evidence now suggests that both IgE and mast cells are also key drivers of the long-term pathophysiological changes and tissue remodeling associated with chronic allergic inflammation in asthma and other settings. Such potential roles include IgE-dependent regulation of mast-cell functions, actions of IgE that are largely independent of mast cells and roles of mast cells that do not directly involve IgE. In this review, we discuss findings supporting the conclusion that IgE and mast cells can have both interdependent and independent roles in the complex immune responses that manifest clinically as asthma and other allergic disorders.
Mast cells and IgE are so inextricably linked to the pathology of allergic disorders, including fatal anaphylaxis, that it can be difficult to think of them in other contexts. Surely, we do not have ...mast cells and IgE so that we can eat a peanut and die! It is thought that mast cells and IgE and basophils (circulating granulocytes, whose functions partially overlap with those of mast cells) can contribute to host defense as components of adaptive T helper cell type 2 immune responses to helminths, ticks, and certain other parasites. Accordingly, it was suggested that allergies are misdirected type 2 immune responses in which IgE antibodies are produced against any of a broad variety of apparently harmless antigens. However, components of animal venoms also can sensitize individuals to develop severe IgE-associated allergic reactions, including fatal anaphylaxis, on subsequent venom exposure. Here, I describe evidence that mast cells can enhance innate host resistance to reptile or arthropod venoms during responses to an initial exposure to such venoms and that acquired type 2 immune responses, IgE antibodies, the high-affinity IgE receptor FcεRI, and mast cells can contribute toward acquired resistance in mice to the lethal effects of honeybee or Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against noxious substances.
Mast cells are widely distributed in tissues, particularly near surfaces exposed to the environment. Mast cells can be activated to secrete diverse mediators and cytokines by IgE and specific Ag and ...many other stimuli, including products derived from either pathogens or the host during innate immune responses. Although mast cells are best known for their role in IgE-associated allergic disorders, mast cells can also exacerbate models of autoimmunity, enhance the sensitization and/or effector phases of certain cutaneous contact hypersensitivity responses, and increase inflammation and mortality during some severe bacterial infections. In other settings, however, mast cells can limit inflammation and tissue injury: mast cells promote host resistance in certain models of bacterial or parasite infection, limit pathology during some acquired immune responses to environmental Ag, including examples of severe contact hypersensitivity, and have adjuvant-like properties that can enhance the development of protective immunity against pathogens. These and other findings suggest that mast cells occupy a critical niche at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may function to perturb or help to restore homeostasis (or both), with consequences that can either promote health or contribute to disease.
Hematopoietic cells, including lymphoid and myeloid cells, can develop into phenotypically distinct 'subpopulations' with different functions. However, evidence indicates that some of these ...subpopulations can manifest substantial plasticity (that is, undergo changes in their phenotype and function). Here we focus on the occurrence of phenotypically distinct subpopulations in three lineages of myeloid cells with important roles in innate and acquired immunity: macrophages, mast cells and neutrophils. Cytokine signals, epigenetic modifications and other microenvironmental factors can substantially and, in some cases, rapidly and reversibly alter the phenotype of these cells and influence their function. This suggests that regulation of the phenotype and function of differentiated hematopoietic cells by microenvironmental factors, including those generated during immune responses, represents a common mechanism for modulating innate or adaptive immunity.
The discovery in 1987/1988 and 1990 of the cell surface receptor KIT and its ligand, stem cell factor (SCF), was a critical achievement in efforts to understand the development and function of ...multiple distinct cell lineages. These include hematopoietic progenitors, melanocytes, germ cells, and mast cells, which all are significantly affected by loss-of-function mutations of KIT or SCF. Such mutations also influence the development and/or function of additional cells, including those in parts of the central nervous system and the interstitial cells of Cajal (which control gut motility). Many other cells can express KIT constitutively or during immune responses, including dendritic cells, eosinophils, type 2 innate lymphoid cells, and taste cells. Yet the biological importance of KIT in many of these cell types largely remains to be determined. We here review the history of work investigating mice with mutations affecting the white spotting locus (which encodes KIT) or the steel locus (which encodes SCF), focusing especially on the influence of such mutations on mast cells. We also briefly review efforts to target the KIT/SCF pathway with anti-SCF or anti-Kit antibodies in mouse models of allergic disorders, parasite immunity, or fibrosis in which mast cells are thought to play significant roles.
Future Needs in Mast Cell Biology Varricchi, Gilda; de Paulis, Amato; Marone, Gianni ...
International journal of molecular sciences,
09/2019, Letnik:
20, Številka:
18
Journal Article
Recenzirano
Odprti dostop
The pathophysiological roles of mast cells are still not fully understood, over 140 years since their description by Paul Ehrlich in 1878. Initial studies have attempted to identify distinct ..."subpopulations" of mast cells based on a relatively small number of biochemical characteristics. More recently, "subtypes" of mast cells have been described based on the analysis of transcriptomes of anatomically distinct mouse mast cell populations. Although mast cells can potently alter homeostasis, in certain circumstances, these cells can also contribute to the restoration of homeostasis. Both solid and hematologic tumors are associated with the accumulation of peritumoral and/or intratumoral mast cells, suggesting that these cells can help to promote and/or limit tumorigenesis. We suggest that at least two major subsets of mast cells, MC1 (meaning anti-tumorigenic) and MC2 (meaning pro-tumorigenic), and/or different mast cell mediators derived from otherwise similar cells, could play distinct or even opposite roles in tumorigenesis. Mast cells are also strategically located in the human myocardium, in atherosclerotic plaques, in close proximity to nerves and in the aortic valve. Recent studies have revealed evidence that cardiac mast cells can participate both in physiological and pathological processes in the heart. It seems likely that different subsets of mast cells, like those of cardiac macrophages, can exert distinct, even opposite, effects in different pathophysiological processes in the heart. In this chapter, we have commented on possible future needs of the ongoing efforts to identify the diverse functions of mast cells in health and disease.
House dust mite-derived proteases contribute to allergic disorders in part by disrupting epithelial barrier function. Interleukin-33 (IL-33), produced by lung cells after exposure to protease ...allergens, can induce innate-type airway eosinophilia by activating natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2), to secrete Th2 type-cytokines. Because IL-33 also can induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are thought to cooperate with NH cells in enhancing protease or IL-33-mediated innate-type airway eosinophilia. However, we found that MC-deficient KitW-sh/W-sh mice exhibited exacerbated protease-induced lung inflammation associated with reduced numbers of regulatory T (Treg) cells. Moreover, IL-2 produced by IL-33-stimulated MCs promoted expansion of numbers of Treg cells, thereby suppressing development of papain- or IL-33-induced airway eosinophilia. We have thus identified a unique anti-inflammatory pathway that can limit induction of innate-type allergic airway inflammation mediated by NH cells.
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•MC-deficient mice exhibit exacerbated papain-induced lung inflammation•Such lung inflammation is associated with reduced numbers of Treg cells•IL-2 produced by IL-33-stimulated mast cells promotes Treg cell expansion•MCs suppress papain-induced airway inflammation by numbers of Treg cells
The role of mast cells (MCs) in non-Th2 cell- and non-IgE-mediated allergic disorders is unknown. Nakae and colleagues show that IL-33-stimulated MC-derived IL-2 enhances expansion of numbers of regulatory T cells, thereby suppressing of allergic inflammation.
Mast cells can function as effector and immunoregulatory cells in immunoglobulin E-associated allergic disorders, as well as in certain innate and adaptive immune responses. This review focuses on ...exciting new developments in the field of mast cell biology published in the past year. We highlight advances in the understanding of FcvarepsilonRI-mediated signaling and mast cell-activation events, as well as in the use of genetic models to study mast cell function in vivo. Finally, we discuss newly identified functions for mast cells or individual mast cell products, such as proteases and interleukin 10, in host defense, cardiovascular disease and tumor biology and in settings in which mast cells have anti-inflammatory or immunosuppressive functions.
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.
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