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Articles by David Breault
Glucocorticoids induce a phagocytic C1Q+ macrophage phenotype primed for IFNγ-dependent CXCL9 secretion
Abstract Glucocorticoids are an emerging component of the tumor microenvironment and play a multifaceted role in modulating immune responses. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by systemic cortisol excess in ~ 60% of cases. Responses to immune checkpoint inhibitors (ICI) in patients with ACC are variable, and currently, no reliable biomarkers exist to predict therapeutic outcomes.
Epigenetic memory of colitis promotes tumour growth
Abstract Chronic inflammation is a well-established risk factor for cancer, but the underlying molecular mechanisms remain unclear1,2. Using a mouse model of colitis, we demonstrate that colonic stem cells retain an epigenetic memory of inflammation following disease resolution that persists for more than 100 days. Here we find that memory of colitis is characterized by a cumulative gain of activator protein 1 (AP-1) transcription factor activity, with durable changes to chromatin accessibility.
The transcription factor HHEX maintains glucocorticoid levels and protects adrenals from androgen-induced lipid depletion - Nature Communications
Abstract Glucocorticoid-producing cells of the adrenal cortex (i.e. zona fasciculata, zF) constitute the critical effectors of the hypothalamic-pituitary-adrenal axis, mediating the mammalian stress response. With glucocorticoids being essential for life, zF dysfunction perturbs multiple organs that participate in optimizing cardiometabolic fitness.
RELMβ sets the threshold for microbiome-dependent oral tolerance - Nature
Abstract Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis1,2. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ)3,4 is a critical regulator of oral tolerance. RELMβ is abundant in the sera of both patients with FA and mouse models of FA.
An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii - npj Biofilms and Microbiomes
Abstract Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner.
Extracellular carriers control lipid-dependent secretion, delivery, and activity of WNT morphogens
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Inflammation-induced adrenal dysfunction - Nature Reviews Endocrinology
Acute inflammation triggers activation of the hypothalamic–pituitary–adrenal axis, but whether it could also impede the adrenocortical response to adrenocorticotropic hormone remains controversial. A new study using preclinical models of acute inflammation demonstrates dysregulation of energy metabolism in adrenocortical cells, resulting in oxidative stress that induces disruption of steroidogenesis. Refers to Mateska, I. et al.
Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice - Nature Communications
Ethical approval declarations Mouse experiments were conducted according to French and European directives for the use and care of animals for research purposes and were approved by the Comité d’Éthique pour l’Expérimentation Animale en Auvergne (project agreement #211522019061912052883), C2EA-02, at Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement, Research Centre Clermont-Theix, France (C2E2A).
Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction - Nature Biomedical Engineering
Abstract Environmental enteric dysfunction (EED)—a chronic inflammatory condition of the intestine—is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption.
A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine - Nature Communications
Abstract Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in an increase in the number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice.
Literary Review of Canada
Get LRC Weekend Free literary snapshots from across Canada. Sign Up! Share This Review Since the beginning, we have had a language debate in Canada. Although there are 7.2 million francophones in this country (roughly 20 percent of the population), the stakes of this perennial debate can seem rather insignificant for anyone living in a predominantly anglophone region. In such a place, the issue can seem rather one-sided, centred on shallow complaints of underrepresentation. Cue the eye roll.
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