Mast cells acquire MHCII from dendritic cells during skin inflammation

Dudeck, Jan; Medyukhina, Anna; Fröbel, Julia; Svensson, Carl-Magnus; Kotrba, Johanna; Gerlach, Michael; Gradtke, Ann-Christine; Schröder, Bernd; Speier, Stephan; Figge, Marc Thilo; Dudeck, Anne

doi:10.1084/jem.20160783

Cited by 57 publications

(58 citation statements)

References 71 publications

(84 reference statements)

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“…Overall, it is interesting to investigate the means through which MCs may take up Ags from their surrounding atherosclerotic environment as, to our knowledge, there are no reports of MCs advancing into a foam cell state. Nonetheless, MCs have been reported in the past to affect intraplaque macrophages (58), whereas they were found to also interact with dendritic cells and actively exchange intracellular material and Ags (59) or even MHC-II molecules (60). In such a way, MCs can shape T cell responses in as much a direct as an indirect manner.…”

Section: Discussionmentioning

confidence: 99%

Hypercholesterolemia Induces a Mast Cell–CD4+ T Cell Interaction in Atherosclerosis

Kritikou

Heijden

Swart

et al. 2019

The Journal of Immunology

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Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4 + T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4 + T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet-fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide-loaded MCs increased OT-II CD4 + T cell proliferation in vitro. The aortic CD4 + and T H1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Hypercholesterolemia Induces a Mast Cell–CD4+ T Cell Interaction in Atherosclerosis

Kritikou

Heijden

Swart

et al. 2019

The Journal of Immunology

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“…Surprisingly, cross-dressing of MCs with fully functional active MHC class II complexes by DCs equipped MCs with antigen-presenting capacity, which subsequently enhanced T cell-driven skin inflammation. 36 Consequently, MCs initiate and orchestrate innate responses and recruitment of additional innate effector cells, as well as promote and regulate adaptive immunity. Here MCs exhibit 3 modes of action: (1) direct antigen-presenting capacities of MCs under certain circumstances, (2) modulation of DC migration and effector T-cell priming efficiency, (3) recruitment of effector T-cell subsets to sites of inflammation or infection and onsite activation of homing T cells to drive efficient inflammatory responses.…”

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confidence: 99%

Mast cells as protectors of health

Dudeck

Köberle

Goldmann

et al. 2019

Journal of Allergy and Clinical Immunology

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100

106

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Mast cells (MCs), which are well known for their effector functions in T H 2-skewed allergic and also autoimmune inflammation, have become increasingly acknowledged for their role in protection of health. It is now clear that they are also key modulators of immune responses at interface organs, such as the skin or gut. MCs can prime tissues for adequate inflammatory responses and cooperate with dendritic cells in T-cell activation. They also regulate harmful immune responses in trauma and help to successfully orchestrate pregnancy. This review focuses on the beneficial effects of MCs on tissue homeostasis and elimination of toxins or venoms. MCs can enhance pathogen clearance in many bacterial, viral, and parasitic infections, such as through Toll-like receptor 2-triggered degranulation, secretion of antimicrobial cathelicidins, neutrophil recruitment, or provision of extracellular DNA traps. The role of MCs in tumors is more ambiguous; however, encouraging new findings show they can change the tumor microenvironment toward antitumor immunity when adequately triggered. Uterine tissue remodeling by a-chymase (mast cell protease [MCP] 5) is crucial for successful embryo implantation. MCP-4 and the tryptase MCP-6 emerge to be protective in central nervous system trauma by reducing inflammatory damage and excessive scar formation, thereby protecting axon growth. Last but not least, proteases, such as carboxypeptidase A, released by FcεRIactivated MCs detoxify an increasing number of venoms and endogenous toxins. A better understanding of the plasticity of MCs will help improve these advantageous effects and hint at ways to cut down detrimental MC actions.

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“…A detailed guide for this procedure is provided in the online documentation (https://applied-systems-biology.github.io/DeconvTest/, https://github.com/applied-systems-biology/DeconvTest/blob/master/docs/DeconvTest_guide_for_microscopy_image_deconvolution.ipynb), whereas here we briefly outline the steps that the users need to undertake to optimally deconvolve their images. As an example, we use a small image volume from intravital two‐photon microscopy imaging of murine ear skin (Figure 5A) .…”

Section: Resultsmentioning

confidence: 99%

DeconvTest: Simulation framework for quantifying errors and selecting optimal parameters of image deconvolution

Medyukhina

Figge

2020

Journal of Biophotonics

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Deconvolution is an essential step of image processing that aims to compensate for the image blur caused by the microscope's point spread function. With many existing deconvolution methods, it is challenging to choose the method and its parameters most appropriate for particular image data at hand. To facilitate this task, we developed DeconvTest: an open-source Python-based framework for generating synthetic microscopy images, deconvolving them with different algorithms, and quantifying reconstruction errors. In contrast to existing software, DeconvTest combines all components required to analyze deconvolution performance in a systematic, high-throughput and quantitative manner. We demonstrate the power of the framework by using it to identify the optimal deconvolution settings for synthetic and real image data. Based on this, we provide a guideline for (a) choosing optimal values of deconvolution parameters for image data at hand and (b) optimizing imaging conditions for best results in combination with subsequent image deconvolution. K E Y W O R D Sdeconvolution, open-source software, performance evaluation

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Mast cells acquire MHCII from dendritic cells during skin inflammation

Cited by 57 publications

References 71 publications

Hypercholesterolemia Induces a Mast Cell–CD4+ T Cell Interaction in Atherosclerosis

Hypercholesterolemia Induces a Mast Cell–CD4+ T Cell Interaction in Atherosclerosis

Mast cells as protectors of health

DeconvTest: Simulation framework for quantifying errors and selecting optimal parameters of image deconvolution

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