Mast cell–associated alveolar inflammation in patients with atopic uncontrolled asthma

Andersson, Cecilia; Bergqvist, Anders; Mori, Masataka; Mauad, Thaís; Bjermer, Leif; Erjefält, Jonas

doi:10.1016/j.jaci.2011.01.022

Cited by 92 publications

(127 citation statements)

References 63 publications

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“…The mature mast cells in sensitized and challenged chimeric CD11c-DTR mice were localized to the alveolar parenchyma. Interestingly, patients with atopic uncontrolled asthma also have more mast cells in the alveolar parenchyma as compared with healthy controls (5). Remarkably, sensitized mice that lacked CD11c + cells during the challenge phase had significantly fewer mast cells 8 d after challenge.…”

Section: Discussionmentioning

confidence: 95%

“…P atients with allergic asthma have a Th2 type of immune response leading to, for example, mucus production, airway hyperresponsiveness, infiltration of inflammatory cells, and increased levels of allergen-specific IgE (1). Tissueresident mast cells are activated and release mediators that participate in the allergic response (2), and the numbers of mature mast cells are increased in the human asthmatic lung (3)(4)(5). In experimental models, mice lacking mast cells have attenuated airway responses, also pointing to an important role for mast cells in the development of allergic asthma (6)(7)(8).…”

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confidence: 99%

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CD11c+ Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung

Dahlin

Feinstein

Cui

et al. 2012

The Journal of Immunology

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Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c+ cells have to be present during the challenge phase for several features of allergic inflammation to occur. Whether CD11c+ cells play a role for Ag-induced increases of lung mast cells is unknown. In this study, we used diphtheria toxin treatment of sensitized CD11c-diphtheria toxin receptor transgenic mice to deplete CD11c+ cells. We demonstrate that recruitment of mast cell progenitors to the lung is substantially reduced when CD11c+ cells are depleted during the challenge phase. This correlated with an impaired induction of endothelial VCAM-1 and led to a significantly reduced number of mature mast cells 1 wk after challenge. Collectively, these data suggest that Ag challenge stimulates CD11c+ cells to produce cytokines and/or chemokines required for VCAM-1 upregulation on the lung endothelium, which in turn is crucial for the Ag-induced mast cell progenitor recruitment and the increase in mast cell numbers.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

CD11c+ Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung

Dahlin

Feinstein

Cui

et al. 2012

The Journal of Immunology

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“…[3][4][5] These mediators are devastating to the asthmatic lung causing, for example, bronchoconstriction. 6,7 In comparison with healthy individuals, the mast cell numbers are increased in the airway smooth muscle 8 and alveolar parenchyma 9 of asthmatics. As a consequence, a high number of mast cells can be activated during allergen exposure, and the symptoms can be severe.…”

Section: Introductionmentioning

confidence: 99%

“…As asthmatics have an increased number of mast cells in the airways, 8,9,40 we determined whether this was reflected by a higher frequency of blood mast cell progenitors in asthmatics than in healthy controls. We conclude that there was no major difference in the frequency of human blood mast cell progenitors between the 10 healthy subjects and 14 asthmatics.…”

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confidence: 99%

“…High alveolar mast cell numbers are found in uncontrolled asthmatics with reduced lung function. 9 Therefore, a high blood mast cell progenitor frequency may reflect ongoing recruitment to the lung resulting in increased mast cell density, which could contribute to the reduced lung function. Quantification of Lin 2 CD34 hi CD117 int/hi FceRI 1 mast cell progenitors may also be clinically important in patients with, for example, mastocytosis and parasitic infections.…”

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Lin− CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors

Dahlin¹,

Malinovschi²,

Öhrvik³

et al. 2016

Blood

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Differential mast cell phenotypes in benign versus cancer tissues and prostate cancer oncologic outcomes

Sullivan

Maynard

Heaphy

et al. 2021

The Journal of Pathology

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We reported previously that high numbers of mast cells in benign (extra‐tumoral) regions of the prostate are associated with worse outcomes after radical prostatectomy including biochemical recurrence and the development of metastases. Herein, with a cohort of 384 men, we performed mast cell subtyping and report that higher minimum number of the tryptase‐only (MCT) subset of extra‐tumoral mast cells is associated with increased risk of biochemical recurrence (comparing highest to lowest tertiles: HR 2.32, 95% CI 1.37–3.93; P‐trend = 0.002), metastases (HR 3.62, 95% CI 1.75–7.47; P‐trend 0.001), and death from prostate cancer (HR 2.87, 95% CI 1.19–6.95; P‐trend = 0.02). Preliminary RNA sequencing and comparison of benign versus cancer tissue mast cells revealed differential expression of additional site‐specific genes. We further demonstrate that the genes CXCR4 and TFE3 are more highly expressed in tumor‐infiltrating mast cells as well as other tumor‐infiltrating immune cells and in tumor cells, respectively, and represent an altered tumor microenvironment. KIT variants were also differentially expressed in benign versus cancer tissue mast cells, with KIT variant 1 (GNNK+) mast cells identified as more prevalent in extra‐tumoral regions of the prostate. Finally, using an established mouse model, we found that mast cells do not infiltrate Hi‐Myc tumors, providing a model to specifically examine the role of extra‐tumoral mast cells in tumorigenesis. Hi‐Myc mice crossed to mast cell knockout (Wsh) mice and aged to 1 year revealed a higher degree of pre‐invasive lesions and invasive cancer in wild‐type mice versus heterozygous and knockout mice. This suggests a dosage effect where higher numbers of extra‐tumoral mast cells resulted in higher cancer invasion. Overall, our studies provide further evidence for a role of extra‐tumoral mast cells in driving adverse prostate cancer outcomes. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Mast cell–associated alveolar inflammation in patients with atopic uncontrolled asthma

Abstract: Our data suggest that patients with atopic uncontrolled asthma have an increased parenchymal infiltration of MC(T) and MC(TC) populations with increased expression of FcεRI and surface-bound IgE compared with atopic and nonatopic controls.

Cited by 92 publications

References 63 publications

CD11c+ Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung

CD11c+ Cells Are Required for Antigen-Induced Increase of Mast Cells in the Lung

Lin− CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors

Differential mast cell phenotypes in benign versus cancer tissues and prostate cancer oncologic outcomes

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