A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice

Sibilano, Riccardo; Gaudenzio, Nicolas; DeGorter, Marianne K.; Reber, Laurent L.; Hernandez, Joseph D.; Starkl, Philipp; Zurek, Oliwia W.; Tsai, Mindy; Zahner, Sonja; Montgomery, Stephen B.; Roers, Axel; Kronenberg, Mitchell; Yu, Mang; Galli, Stephen J.

doi:10.1038/ncomms13696

Cited by 28 publications

(21 citation statements)

References 56 publications

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“…122 In addition, TNF receptor superfamily member 14 (TNFRSF14) activation by its ligand TNF SF14 123 enhances FcεRI signaling and results in enhanced degranulation of human and mouse mast cells. 124 IL-6 increases the reactivity of human mast cells to FcεRI cross-linking. 125 Similarly, IL-33 increases IgE-mediated secretion in human mast cells.…”

Section: Co-activation Of Receptorsmentioning

confidence: 97%

Human mast cells and basophils—How are they similar how are they different?

Varricchi

Raap

Rivellese

et al. 2018

Immunological Reviews

112

104

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Mast cells and basophils are key contributors to allergies and other inflammatory diseases since they are the most prominent source of histamine as well as numerous additional inflammatory mediators which drive inflammatory responses. However, a closer understanding of their precise roles in allergies and other pathological conditions has been marred by the considerable heterogeneity that these cells display, not only between mast cells and basophils themselves but also across different tissue locations and species. While both cell types share the ability to rapidly degranulate and release histamine following high-affinity IgE receptor cross-linking, they differ markedly in their ability to either react to other stimuli, generate inflammatory eicosanoids or release immunomodulating cytokines and chemokines. Furthermore, these cells display considerable pharmacological heterogeneity which has stifled attempts to develop more effective anti-allergic therapies. Mast cell- and basophil-specific transcriptional profiling, at rest and after activation by innate and adaptive stimuli, may help to unravel the degree to which these cells differ and facilitate a clearer understanding of their biological functions and how these could be targeted by new therapies.

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Section: Co-activation Of Receptorsmentioning

confidence: 97%

Human mast cells and basophils—How are they similar how are they different?

Varricchi

Raap

Rivellese

et al. 2018

Immunological Reviews

112

104

View full text Add to dashboard Cite

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“…LIGHT-HVEM interaction does not impact the development of experimental cerebral malaria, while local LTα drives cerebral pathology ( 13 , 14 ). HVEM is an important co-stimulatory receptor expressed by T and B cells, endothelial cells and mast cells ( 15 – 18 ). HVEM-signaling enhances the expansion of T cells and is required for the persistence of memory T cells in bacterial and viral infections and in experimental settings of challenge with model antigen ( 19 – 22 ).…”

Section: Introductionmentioning

confidence: 99%

HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage

et al. 2018

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CD8+ T cells are key players during infection with the malaria parasite Plasmodium berghei ANKA (PbA). While they cannot provide protection against blood-stage parasites, they can cause immunopathology, thus leading to the severe manifestation of cerebral malaria. Hence, the tight control of CD8+ T cell function is key in order to prevent fatal outcomes. One major mechanism to control CD8+ T cell activation, proliferation and effector function is the integration of co-inhibitory and co-stimulatory signals. In this study, we show that one such pathway, the HVEM-CD160 axis, significantly impacts CD8+ T cell regulation and thereby the incidence of cerebral malaria. Here, we show that the co-stimulatory molecule HVEM is indeed required to maintain CD8+ T effector populations during infection. Additionally, by generating a CD160−/− mouse line, we observe that the HVEM ligand CD160 counterbalances stimulatory signals in highly activated and cytotoxic CD8+ T effector cells, thereby restricting immunopathology. Importantly, CD160 is also induced on cytotoxic CD8+ T cells during acute Plasmodium falciparum malaria in humans. In conclusion, CD160 is specifically expressed on highly activated CD8+ T effector cells that are harmful during the blood-stage of malaria.

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“…77 Mast cells have been linked to induction of allergic airway disease in mice, although this was shown to depend on the experimental model. [78][79][80] In this context we were able to demonstrate that in previously sensitized mice mast cells can promote migration of antigenladen APCs from the lung to the draining lymph nodes on intranasal antigen challenge. 67 Accordingly, in the absence of mast cells, airway inflammation, mucus production, and airway hyperreactivity were all decreased.…”

Section: Effect Of Mast Cells On Professional Apcs In Models For Vaccmentioning

confidence: 87%

Mast cells within cellular networks

Stassen

Hartmann

Delgado

et al. 2019

Journal of Allergy and Clinical Immunology

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Mast cells are highly versatile in terms of their mode of activation by a host of stimuli and their ability to flexibly release a plethora of biologically highly active mediators. Within the immune system, mast cells can best be designated as an active nexus interlinking innate and adaptive immunity. Here we try to draw an arc from initiation of acute inflammatory reactions to microbial pathogens to development of adaptive immunity and allergies. This multifaceted nature of mast cells is made possible by interaction with multiple cell types of immunologic and nonimmunologic origin. Examples for the former include neutrophils, eosinophils, T cells, and professional antigenpresenting cells. These interactions allow mast cells to orchestrate inflammatory innate reactions and complex adaptive immunity, including the pathogenesis of allergies. Important partners of nonimmunologic origin include cells of the sensory neuronal system. The intimate association between mast cells and sensory nerve fibers allows bidirectional communication, leading to neurogenic inflammation. Evidence is accumulating that this mast cell/nerve crosstalk is of pathophysiologic relevance in patients with allergic diseases, such as asthma.

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A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice

Cited by 28 publications

References 56 publications

Human mast cells and basophils—How are they similar how are they different?

Human mast cells and basophils—How are they similar how are they different?

HVEM and CD160: Regulators of Immunopathology During Malaria Blood-Stage

Mast cells within cellular networks

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