The Multitasking Mast Cell: Positive and Negative Roles in the Progression of Autoimmunity

Christy, Alison; Brown, Melissa A.

doi:10.4049/jimmunol.179.5.2673

Cited by 62 publications

(39 citation statements)

References 113 publications

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“…Our studies of the roles of mast cells in various cutaneous or pulmonary responses, and work by others with mast cell knock-in mice showing that mast cells can contribute to the development of pathology in models of EAE [27] or antibody-dependent arthritis [50], strongly suggest that mast cells can contribute to tissue damage and tissue remodeling in various anatomical sites via multiple direct or indirect mechanisms, and can be activated to express such functions by different potential stimuli in different settings.…”

Section: Mast Cell-dependent Tissue Remodeling In a Mouse Model Of Chmentioning

confidence: 62%

“…Many of these products are regarded as "pro-inflammatory" in that, individually or in concert, they can elicit features of inflammation that are observed in settings of acute and/or chronic inflammation, e.g., vasodilatation, plasma extravasation and the recruitment and activation of granulocytes (i.e., neutrophils, eosinophils and basophils), T cells, B cells, dendritic cells and monocytes [4,8,9,27,28]. Mast cell products also can promote changes in the tissues that are affected by such inflammatory responses, including the local degradation or remodelling of structural elements of the tissues, which can be associated with significant changes in the function of the affected organs [29][30][31].…”

Section: Mast Cell Activation and Secreted Productsmentioning

confidence: 99%

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Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

Galli

Tsai

2008

Journal of Dermatological Science

227

199

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SummaryThe possible roles of mast cells in heath and disease have been a topic of interest for over one hundred and twenty five years. Many adaptive or pathological processes affecting the skin or other anatomical sites have been associated with morphological evidence of mast cell activation, and/or with changes in mast cell numbers or phenotype. Such observations, taken together with the known functions of the diverse mediators, cytokines and growth factors which can be secreted by mast cells, have suggested many potential functions for mast cells in health and disease. Definitively identifying the importance of mast cells in biological responses in humans is difficult. However, mutant mice which are profoundly mast cell-deficient, especially those which can undergo engraftment with wild type or genetically-altered mast cells, provide an opportunity to investigate the importance of mast cells, and specific mast cell functions or products, in various adaptive or pathological responses in mice. Such work has shown that mast cells can significantly influence multiple features of inflammatory or immune responses, through diverse effects that can either promote or, surprisingly, suppress, aspects of these responses. Through such functions, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis.

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Section: Mast Cell-dependent Tissue Remodeling In a Mouse Model Of Chmentioning

confidence: 62%

Section: Mast Cell Activation and Secreted Productsmentioning

confidence: 99%

Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

Galli

Tsai

2008

Journal of Dermatological Science

227

199

View full text Add to dashboard Cite

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“…Treatments targeting mast cells have been investigated for use in some autoimmue diseases [156,157 {Theoharides, 2015 #233], drugs considered to 'stabilize' mast cells (for example, cromolyn sodium) have been showed ameliorating disease severity in EAE. [158]. Use of anti-histamines as an adjunct treatment in AA has been suggested [15].…”

Section: Activation Of Mast Cells In Alopecia Areata Initiation and Pmentioning

confidence: 99%

The role of lymphocytes in the development and treatment of alopecia areata

Guo

Cheng

Shapiro

et al. 2015

Expert Review of Clinical Immunology

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SummaryAlopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri-and intra-follicular regions, and hair follicle disruption. Both CD4+ and CD8+ lymphocytes are abundant in AA lesions; however, CD8+ cytotoxic T lymphocytes are more likely to enter inside hair follicles, circumstantially suggesting that they have a significant role to play in AA development. Several rodent models recapitulate important features of the human autoimmune disease and demonstrate that CD8+ cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation. However, the initiating events, the selfantigens involved, and the molecular signaling pathways, all need further exploration. Studying CD8+ cytotoxic T lymphocytes and their fate decisions in AA development may reveal new and improved treatment approaches.

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“…Increased tissue levels of histamine correlate with the onset of EAE (6)(7)(8). Mast cells, the major source of histamine (9), are present in MS lesions (10)(11)(12), and evidence of mast cell activation is found in the cerebrospinal fluid (CSF) of patients who have MS (13). In mice, mast cells (14) and their activation (15) are required for early EAE onset and maximal disease severity.…”

mentioning

confidence: 99%

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Lu¹,

Diehl²,

Noubade³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Disruption of the blood-brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeability. B. pertussis-induced histamine sensitization (Bphs) T he blood-brain barrier (BBB) involves endothelial cells that line the blood vessels of the central nervous system (CNS) and the tight junction protein complexes between these endothelial cells. The BBB thereby acts as a physical and metabolic barrier by separating the vasculature from the parenchyma of the CNS (1). Breakdown of the BBB is associated with the onset and pathogenesis of multiple sclerosis (MS), a degenerative, demyelinating, inflammatory disease of the CNS (2). In MS and its autoimmune model, experimental autoimmune encephalomyelitis (EAE), activated T cells cross the BBB into the perivascular space of the CNS, causing damage to neurons (2). Surveillance of the CNS by T cells does occur (3), but the paucity of leukocytes found in the CNS under noninflammatory conditions suggests that extravasation of cells across the BBB is tightly regulated. Therefore, identifying factors that modulate BBB permeability may be of therapeutical value in treating inflammatory demyelinating diseases of the CNS.Bordetella pertussis-induced hypersensitivity to histamine (Bphs/ Bphs) is a genetically controlled intermediate phenotype associated with susceptibility to EAE (4). Bphs is a state wherein mice are rendered highly susceptible to histamine after a preceding injection of B. pertussis toxin (PTX) (5). Bphs-susceptible strains of mice die within 30 min after histamine challenge, presumably attributable to hypotensive and hypovolemic shock. The cells targeted during Bphs are not known. Histamine has also been implicated in the pathophysiology of MS and EAE. Increased tissue levels of histamine correlate with the onset of EAE (6-8). Mast cells, the major source of histamine (9), are present in MS lesions (10-12), and evidence of mast cell activation is found in the cerebrospinal fluid (CSF) of patients who have MS (13). In mice, mast cells (14) and their activation (15) are required for early EAE onset and maximal disease severity.The effects of histamine are mediated by four surface histamine receptors: H 1 R, H 2 R, H 3 R, and H 4 R (16). H 1 R protein and mRNA are highly expressed in MS lesions (17), and H 1 antihistamines reduce EAE in mice and rats (17,18). In patients with MS, the use of sedating H 1 antihistamines is correlated with decreased disease incidence and amelioration of symptoms (19,20). Our laboratory has shown that susceptibility to Bphs and EAE requires expression of Hrh1, the gene encoding H 1 R (21).Expression of H 1 R on T cells is required for their full encephalitogenic potential (22), but the contribution of H 1 R signaling in other cell types to the pathogenesis of EAE has not been formally addressed. In this study, w...

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The Multitasking Mast Cell: Positive and Negative Roles in the Progression of Autoimmunity

Cited by 62 publications

References 113 publications

Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

The role of lymphocytes in the development and treatment of alopecia areata

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

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The Multitasking Mast Cell: Positive and Negative Roles in the Progression of Autoimmunity

Cited by 62 publications

References 113 publications

Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis

The role of lymphocytes in the development and treatment of alopecia areata

Endothelial histamine H 1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

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Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis