Dermal Extracellular Matrix-Derived Hydrogels as an <i>In Vitro</i> Substrate to Study Mast Cell Maturation

Ozpinar, Emily W; Frey, Ariana L; Arthur, Greer; Mora-Navarro, Camilo; Biehl, Andreea; Snider, Douglas B.; Cruse, Glenn; Freytes, Donald O.

doi:10.1089/ten.tea.2020.0142

Cited by 18 publications

(10 citation statements)

References 86 publications

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“…1c, d). Similar to a previous study utilizing human mast cell lines to study the influence of decellularized ECM on mast cell viability 13 , interaction of differentiated bone marrow derived FcƐRI + c-kit + mast cells (Supplementary Fig. 2) with the ECM hydrogel material in solution at non-gelling concentrations in comparison to collagen and media only controls showed higher alamarBlue TM readings, thus, confirming matrix interaction enhanced differentiated mast cell viability (Supplementary Fig.…”

Section: Results: Mast Cell Recruitment and Degranulation In Vivo In Response To Ecm Biomaterialssupporting

confidence: 82%

“…Although this induced response has been rigorously evaluated with macrophage 7,9 and T cell populations 10,11 , potential contribution of mast cells to the immunomodulatory effect of naturally derived biomaterials has been largely ignored and under investigated 12 . In vitro culture of human mast cell lines has demonstrated that interaction in the decellularized extracellular matrix (ECM) microenvironment promotes mast cell differentiation, maturation, and viability compared to collagen controls 13 . However, in vivo studies have mainly just evaluated shifts in mast cell numbers associated with biomaterial deployment, though their general low numbers in tissue make it difficult to determine conclusive results from this approach 14,15 .…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory Contribution of Mast Cells to the Regenerative Biomaterial Microenvironment

Wang

Mesfin

Ungerleider

et al. 2020

Preprint

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Regulation of the immune response contributes to the severity and outcomes in various disease conditions. Bioactive immunomodulatory biomaterials have shown promise for influencing these responses to promote tissue repair and regeneration. In this study, we investigated the role of mast cells in the regulation of the immune response to biomaterial scaffolds. In mast cell-deficient mice, there was dysregulation of the expected M1 to M2 macrophage transition typically induced by the biomaterial scaffold. Polarization progression deviated in a gender specific manner with an early transition to an M2 profile in female mice, while the male response was unable to properly transition past a pro-inflammatory M1 state. Both were reversed with mast cell adoptive transfer. Further investigation of the later stage immune response in male mice determined a sustained pro-inflammatory gene expression profile in deficient mice consisting of members from the IL-1 cytokine family and related downstream pathways. As mast cells were mainly associated with detrimental pro-inflammatory outcomes for biomaterial scaffolds, these results demonstrate their contribution to induced immunomodulatory therapies and support their potential as a critical immune regulatory element that can be manipulated for stimulating endogenous tissue repair.

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Section: Results: Mast Cell Recruitment and Degranulation In Vivo In Response To Ecm Biomaterialssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Contribution of Mast Cells to the Regenerative Biomaterial Microenvironment

Wang

Mesfin

Ungerleider

et al. 2020

Preprint

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“…Other factors that could regulate these processes and may hinder research into different FcεRI complexes that exist in human and mouse cells may reside in the tissue microenvironment, where human studies become more difficult to replicate in vitro. In such a setting, perhaps utilizing innovative extracellular matrix-based models, which create a more physiologically relevant environment for cells in vitro could help overcome shortcomings of rodent models [ 55 ]. However, even given these shortcomings, it is clear that, in mast cells and basophils, the unique role of FcεRIβ in cell activation and pro-inflammatory mediator release makes it a relatively cell-specific target, and one with the potential to dampen mast cell responses in allergic inflammation.…”

Section: Fcεri Structure and Functionmentioning

confidence: 99%

Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation

Arthur

Cruse

2022

IJMS

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Mast cells are tissue-resident immune cells that function in both innate and adaptive immunity through the release of both preformed granule-stored mediators, and newly generated proinflammatory mediators that contribute to the generation of both the early and late phases of the allergic inflammatory response. Although mast cells can be activated by a vast array of mediators to contribute to homeostasis and pathophysiology in diverse settings and contexts, in this review, we will focus on the canonical setting of IgE-mediated activation and allergic inflammation. IgE-dependent activation of mast cells occurs through the high affinity IgE receptor, FcεRI, which is a multimeric receptor complex that, once crosslinked by antigen, triggers a cascade of signaling to generate a robust response in mast cells. Here, we discuss FcεRI structure and function, and describe established and emerging roles of the β subunit of FcεRI (FcεRIβ) in regulating mast cell function and FcεRI trafficking and signaling. We discuss current approaches to target IgE and FcεRI signaling and emerging approaches that could target FcεRIβ specifically. We examine how alternative splicing of FcεRIβ alters protein function and how manipulation of splicing could be employed as a therapeutic approach. Targeting FcεRI directly and/or IgE binding to FcεRI are promising approaches to therapeutics for allergic inflammation. The characteristic role of FcεRIβ in both trafficking and signaling of the FcεRI receptor complex, the specificity to IgE-mediated activation pathways, and the preferential expression in mast cells and basophils, makes FcεRIβ an excellent, but challenging, candidate for therapeutic strategies in allergy and asthma, if targeting can be realized.

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“…Echoing the importance of the microenvironment to mast cell differentiation and functional responses, the culture of normally unresponsive mast cells in fibronectin or with fibroblasts has been shown to induce sensitivity to polybasic stimuli (38). Development of complex, yet more physiologically relevant mast cell culture systems (39), as well as proteomic (32) and transcriptomic (31,33) characterisation from patient tissue samples will assist with better understanding the regulation of mast cell MRGPRX2 expression in vivo.…”

Section: Elevated And/or Expanded Expression or Function Of Mrgprx2 In Mast Cellsmentioning

confidence: 99%

Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target

et al. 2021

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Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings.

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Dermal Extracellular Matrix-Derived Hydrogels as an In Vitro Substrate to Study Mast Cell Maturation

Cited by 18 publications

References 86 publications

Immunomodulatory Contribution of Mast Cells to the Regenerative Biomaterial Microenvironment

Immunomodulatory Contribution of Mast Cells to the Regenerative Biomaterial Microenvironment

Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation

Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target

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