Secreted Factors from Human Mast Cells Trigger Inflammatory Cytokine Production by Human Airway Smooth Muscle Cells

Xia, Yu; Harris, Trudi; Stewart, Alastair G.; Mackay, Graham A.

doi:10.1159/000339697

Cited by 17 publications

(21 citation statements)

References 100 publications

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“…By using the human mast cell line HMC [178] to model human mast cell function, it was demonstrated that the release of mast cell mediators stimulates human airway smooth muscle cells to elicit production of proinflammatory cytokines that may lead to the exacerbation of airway inflammation in asthma [179]. Of interest in that respect, recent reports show that histamine downregulates the production of the Th1-associated chemokine IFN-γ-induced protein 10 in myeloid DC and monocytes [180].…”

Section: T Cell Model Systems For Allergy Researchsupporting

confidence: 91%

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Neunkirchner

Schmetterer

Pickl

2014

Int Arch Allergy Immunol

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During the last decades, a multitude of studies applying distinct in vitro and in vivo model systems have contributed greatly to our better understanding of the initiation and regulation of inflammatory processes leading to allergic diseases. Over the years, it has become evident that among lymphocytes, not only IgE-producing B cells and allergy-orchestrating CD4⁺ helper cells but also cytotoxic CD8⁺ T cells, γδ-T cells and innate lymphoid cells, as well as regulatory lymphocytes, might critically shape the immune response towards usually innocuous allergens. In this review, we provide a historic overview of pioneering work leading to the establishment of important lymphocyte-based model systems for allergy research. Moreover, we contrast the original findings with our currently more refined knowledge to appreciate the actual validity of the respective models and to reassess the conclusions obtained from them. Conflicting studies and interpretations are identified and discussed. The tables are intended to provide an easy overview of the field not only for scientists newly entering the field but also for the broader readership interested in updating their knowledge. Along those lines, herein we discuss in vitro and in vivo approaches to the investigation of lymphocyte effector cell activation, polarization and regulation, and describe depletion and adoptive transfer models along with gene knockout and transgenic (tg) methodologies. In addition, novel attempts to establish humanized T cell antigen receptor tg mouse models for allergy research are described and discussed.

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Section: T Cell Model Systems For Allergy Researchsupporting

confidence: 91%

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Neunkirchner

Schmetterer

Pickl

2014

Int Arch Allergy Immunol

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“…Moreover, these exosomes can induce lymphocyte stimulation and proliferation, leading to the production of IL-2, IL-12, and IFN-γ (but not IL-4), and Th1 responses (61). Moreover, these exosomes induce the production of pro-inflammatory cytokines such as IL-6 and IL-8 that are released from human airway smooth muscle cells (ASMCs), exacerbating airway inflammation and recruiting inflammatory cells that perpetuate asthmatic symptoms (5). Finally, MC-derived exosomes induce phenotypic functional maturation of DCs in vivo and in vitro , improving the immune response (62).…”

Section: Exosomes In Asthma and Allergymentioning

confidence: 99%

Novel Modulators of Asthma and Allergy: Exosomes and MicroRNAs

et al. 2017

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Intercellular communication is crucial to the immune system response. In the recent years, the discovery of exosomes has changed the way immune response orchestration was understood. Exosomes are able to operate as independent units that act as mediators in both physiological and pathological conditions. These structures contain proteins, lipidic mediators, and nucleic acids and notoriously include microRNAs (miRNAs). miRNAs are short RNA sequences (around 19–22 nucleotides) with a high phylogenetic conservation and can partially or totally regulate multiple mRNAs, inhibiting protein synthesis. In respiratory diseases such as asthma and allergic sensitization, exosomes released by several cell types and their specific content perform crucial functions in the development and continuation of the pathogenic mechanisms. Released exosomes and miRNAs inside them have been found in different types of clinical samples, such as bronchoalveolar lavage fluids and sputum supernatants, providing new data about the environmental factors and mediators that participate in the inflammatory responses that lead to the exacerbation of asthma. In this review, we summarize our current knowledge of the role of exosomes and miRNAs in asthma and allergic sensitization, paying attention to the functions that both exosomes and miRNAs are described to perform through the literature. We review the effect of exosomes and miRNAs in cells implicated in asthma pathology and the genes and pathways that they modify in them, depicting how their behavior is altered in disease status. We also describe their possible repercussion in asthma diagnosis through their possible role as biomarkers. Therefore, both exosomes and miRNAs can be viewed as potential tools to be added to the arsenal of therapeutics to treat this disease.

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“…These include: T cell exosome activation of mast cells [66,67], and mast cell activation of T and B cells [71,72], mast cell exosome-mediated phenotypic and functional maturation of DC [61,62] and endothelial cells [73], or other mast cells or progenitor stem cells [74]. These effects can be induced via exosome transmitted cytokines [66,75] or mast cell exosome transfer of mRNA encoding the cytokines [37], and by affecting cytokine signaling [75] or triggering cytokine production by bronchial cells [76] or by airway smooth muscle cells [77]. Finally, mast cell exosomes induce phenotypic and functional maturation of DC enabling them to elicit specific immune responses in vivo [78], they activate endothelial cells to secrete clotting factors [73] and can activate T and B cells [79,80].…”

Section: Effects Of Exosome Intercellular Interactions On Allergy Andmentioning

confidence: 99%

“…Further, among the increased numbers of exosomes in airways of mice with a model of asthma, the bronchoepithelial cell-derived exosomes stimulated by IL-13 induce activation of macrophages [77], and exosomes play a role in Th2 cell activation of auxiliary cells [77,78], acting via specific cell surface cytokine receptors, such as IL-4 receptor. This seems to influence triggering of established intracellular signaling pathways that regulate gene expression of Th2 responses.…”

Section: Effects Of Exosome Intercellular Interactions On Allergy Andmentioning

confidence: 99%

Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

Nazimek

Bryniarski²,

Askenase³

2016

Int Arch Allergy Immunol

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Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation.

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Secreted Factors from Human Mast Cells Trigger Inflammatory Cytokine Production by Human Airway Smooth Muscle Cells

Cited by 17 publications

References 100 publications

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Lymphocyte-Based Model Systems for Allergy Research: A Historic Overview

Novel Modulators of Asthma and Allergy: Exosomes and MicroRNAs

Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

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