The Ingenious Mast Cell: Contemporary insights into mast cell behavior and function

Dahlin, Joakim S.; Maurer, Marcus; Metclafe, Dean; Pejler, Gunnar; Sagi‐Eisenberg, Ronit; Nilsson, Gunnar

doi:10.22541/au.160390266.66559016/v1

Cited by 13 publications

(21 citation statements)

References 130 publications

(147 reference statements)

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“…Human mast cells, first described by Paul Ehrlich, are multifunctional immune cells of myeloid lineage, intimately involved in allergic reactions [ 1 , 2 , 3 , 5 , 32 , 33 ]. Mast cells originate from CD34 + /CD117 + /CD13 + multipotent, hematopoietic progenitors [ 4 , 5 ].…”

Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

“…Mast cell activation can occur following many triggers and via a plethora of cell surface receptors, including receptors for IgE, IgG, complement, cytokines, growth factors, stem cell factor, and neuropeptides (beyond the scope of this review) [ 4 , 11 , 33 ]. The prototypic IgE-mediated activation ( Figure 1 ) occurs when allergen specific IgE is bound by a multivalent allergen and interacts with the high affinity receptor for immunoglobulin E (FcεR1) carried on their surfaces [ 44 , 45 ].…”

Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

“…Some pivotal cell surface receptors include those for cytokines (IL-33, IL-12, IL-10, interferon gamma/IFNγ), chemokines (CCR1-CCR7, CXCR1-6), complement (C3a/C5a, CR1-5), Toll-like receptors (TLR 1-6), histamine, prostaglandin, stem cell factor, and IgE [ 4 ]. Descriptions of these receptors and their functions are beyond the scope of this review [ 4 , 33 , 45 , 53 ].…”

Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

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Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Jackson

Pratt

Rupprecht

et al. 2021

IJMS

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Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify the classification of mast cell disorders, point to molecular aspects of mast cell signaling, elucidate underlying genetic defects, and provide approaches to targeted therapies that may benefit such patients.

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Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

Section: Brief Overview Of Mast Cell Biologymentioning

confidence: 99%

See 1 more Smart Citation

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Jackson

Pratt

Rupprecht

et al. 2021

IJMS

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“…Mast cells are part of the innate immune system, acting as first-line sentinels for environmental antigens, but also provide a link to the adaptive immune system by secreting chemokines that recruit CD8+ T-cells to sites of infection ( Podlech et al., 2015 ; Dahlin et al., 2021 ). Schmiedeke et al.…”

Section: Innate and Adaptive Immune Control Of CMV Pathogenesismentioning

confidence: 99%

Editorial: Cytomegalovirus Pathogenesis and Host Interactions

Poole

Nevels

2021

Front. Cell. Infect. Microbiol.

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Editorial on the Research Topic Cytomegalovirus Pathogenesis and Host Interactions SCOPE OF THE RESEARCH TOPICHuman cytomegalovirus (HCMV) is a very widespread and highly prevalent b-herpesvirus, which sometimes causes mononucleosis following primary infection but is rarely associated with severe disease in immunocompetent individuals (Boeckh and Geballe, 2011;Griffiths et al., 2015). However, like all herpesviruses, HCMV establishes infections that last for the life of the host in part by residing in a dormant state referred to as 'latency ' (Sinclair and Poole, 2014;Dupont and Reeves, 2016). Reactivation from latency or primary infection can cause debilitating damage in unborn children or life-threatening disease in immunosuppressed patients including recipients of solid organ or hematopoietic cell transplants (Collins-McMillen et al., 2018;Heald-Sargent et al., 2020). Besides human cell culture systems of HCMV productive and latent infection (Peppenelli et al., 2021;Poole et al., 2021), mice infected with murine cytomegalovirus (MCMV) have served as invaluable models to understand host immune responses, viral immune evasion strategies and the mechanisms of pathogenesis (Brizic et al., 2018;Reddehase and Lemmermann, 2018). HCMV replicates productively in a wide variety of terminally differentiated cell types ('lytic' infection) while targeting select undifferentiated cells, including myeloid progenitors and monocytes, for latent infection (Sinclair and Poole, 2014;Goodrum, 2016). CMVs are highly sophisticated pathogens encoding hundreds of proteins and non-coding RNAs that engage in a myriad of host interactions (Stern-Ginossar et al., 2012;Weekes et al., 2014). The study of these interactions is constantly revealing new and surprising insights into both the replication and persistence strategies of the virus as well as the biology of the host cell and organism.The recently published Research Topic 'Cytomegalovirus Pathogenesis and Host Interactions' combines 28 articles (8 Original Research Articles, 10 Brief Research Reports, 8 Reviews, 1 Mini Review and this Editorial), involving 138 authors, 45 reviewers and 5 editors working in the field. Below, we are providing an overview of the articles published in this Research Topic, dividing them into the four sections 'innate and adaptive immune control of CMV pathogenesis' (11 articles), 'host interactions during CMV latency and reactivation' (6 articles), 'host interactions during productive CMV infection' (6 articles) and 'targeting CMV pathogenesis by anti-viral therapy' (4 articles).

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“…Mast cells contribute to the pathogenesis of various diseases including allergies, asthma, and mastocytosis ( 1 ). One of the mast cells’ main responses follows IgE-allergen immune complex crosslinking of the high-affinity IgE receptors, FcεRI, on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptomics reveals the identity and regulators of human mast cell progenitors

Boey

Bril

et al. 2021

Preprint

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Mast cell accumulation is a hallmark of a number of diseases including allergic asthma and systemic mastocytosis. IgE-mediated crosslinking of the FcϵRI receptors causes mast cell activation and contributes to disease pathogenesis. The mast cell lineage is one of the least studied among the hematopoietic cell lineages and there are still controversies about the identity of the mast cell progenitor, i.e., whether FcϵRI expression appears during the hematopoietic progenitor stage or in maturing mast cells. Here, we used single-cell transcriptomics to reveal a temporal association between the appearance of FcϵRI and the mast cell gene signature in CD34+ hematopoietic progenitors. In agreement with these data, the FcϵRI+ hematopoietic progenitors formed morphologically, phenotypically and functionally mature mast cells in long-term culture assays. Single-cell transcriptomics analysis further revealed the expression patterns of prospective cytokine receptors regulating mast cell progenitor development. Culture assays showed that IL-3 and IL-5 promoted disparate effects on progenitor cell proliferation and survival, respectively, whereas IL-33 caused robust FcϵRI downregulation. Taken together, we have demonstrated that FcϵRI appears during the hematopoietic progenitor stage of mast cell differentiation and that external stimuli may regulate the FcϵRI expression. Thus, the results resolve the controversy regarding the appearance of FcϵRI during mast cell development.

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The Ingenious Mast Cell: Contemporary insights into mast cell behavior and function

Cited by 13 publications

References 130 publications

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Editorial: Cytomegalovirus Pathogenesis and Host Interactions

Single-cell transcriptomics reveals the identity and regulators of human mast cell progenitors

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