Stephen E. Girardin
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View article: Endothelial cell-intrinsic NOD2 signaling regulates the intestinal immune response through the generation of effector and memory T cells
Endothelial cell-intrinsic NOD2 signaling regulates the intestinal immune response through the generation of effector and memory T cells Open
Summary Crohn’s disease (CD) is marked by vascular endothelial dysfunction and aberrant T cell immunity in the gastrointestinal tract. However, mechanistic understanding is lacking of how CD-associated gene variants, particularly those tha…
View article: The innate immune receptor NLRX1 is a novel required modulator for mPTP opening: implications for cardioprotection
The innate immune receptor NLRX1 is a novel required modulator for mPTP opening: implications for cardioprotection Open
View article: Author Correction: Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium
Author Correction: Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium Open
View article: The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury
The IL-18 receptor is expressed on murine small-intestinal enterochromaffin cells and executes a recovery program upon injury Open
Upon injury, epithelial-derived IL-18 is released and induces an inflammatory response in underlying IL18R1 + lamina propria cells. Notably, Il18r1 is also predicted to be expressed and functional in intestinal epithelial cells (IECs), sin…
View article: Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium
Gasdermin-D pores induce an inactivating caspase-4 cleavage that limits IL-18 production in the intestinal epithelium Open
View article: Activation of the NLRP1B inflammasome by caspase-8
Activation of the NLRP1B inflammasome by caspase-8 Open
View article: The conceptual foundations of innate immunity: Taking stock 30 years later
The conceptual foundations of innate immunity: Taking stock 30 years later Open
While largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding of immunology. Innate immunity provides the first barrier to infectio…
View article: Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway
Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway Open
View article: A60 INVESTIGATING THE ROLE OF NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN (NOD) PROTEINS DURING BACTERIAL INFECTIONS IN INTESTINAL EPITHELIAL CELLS
A60 INVESTIGATING THE ROLE OF NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN (NOD) PROTEINS DURING BACTERIAL INFECTIONS IN INTESTINAL EPITHELIAL CELLS Open
Background Inflammatory bowel disease (IBD) is a collection of conditions that result in the inflammation of the gastrointestinal tract causing diarrhea, abdominal pain, weight loss, nausea, and vomiting. With its prevalence a whopping 0.6…
View article: A30 MICROBIOTA AND NOD2 REGULATE SMALL INTESTINAL RESTITUTION THROUGH FETAL-LIKE INTESTINAL STEM CELLS
A30 MICROBIOTA AND NOD2 REGULATE SMALL INTESTINAL RESTITUTION THROUGH FETAL-LIKE INTESTINAL STEM CELLS Open
Background Inflammatory bowel disease is characterized by chronic inflammation of the gastrointestinal tract, resulting in recurrent injury to the intestinal epithelium. Restitution of the small intestinal epithelium is a coordinated respo…
View article: A61 ELUCIDATING INTESTINAL EPITHELIAL INFLAMMASOME MECHANISMS THAT REPAIR THE MUCOSAL BARRIER DURING ENTERIC INFECTION
A61 ELUCIDATING INTESTINAL EPITHELIAL INFLAMMASOME MECHANISMS THAT REPAIR THE MUCOSAL BARRIER DURING ENTERIC INFECTION Open
Background To protect the gastrointestinal tract from infection, intestinal epithelial cells (IECs) lining the mucosa possess cytosolic complexes called inflammasomes which detect pathogenic insult and rapidly initiate inflammation to stop…
View article: A193 DECIPHERING THE INFLUENCE OF CROHN’S DISEASE-ASSOCIATED GENETIC RISK FACTOR, <i>NOD2</i> IN INTESTINAL FIBRO-STENOSIS
A193 DECIPHERING THE INFLUENCE OF CROHN’S DISEASE-ASSOCIATED GENETIC RISK FACTOR, <i>NOD2</i> IN INTESTINAL FIBRO-STENOSIS Open
Background Intestinal fibrosis (IF) is a common debilitating complication associated with Crohn’s disease (CD), an idiopathic inflammatory bowel disease (IBD). IF results in severe strictures that affect the entire gastrointestinal tract, …
View article: A25 DETECTION OF BACTERIAL ADP-HEPTOSE BY INTESTINAL STEM CELLS DRIVES EPITHELIAL REGENERATION FROM PANETH CELL DEDIFFERENTIATION
A25 DETECTION OF BACTERIAL ADP-HEPTOSE BY INTESTINAL STEM CELLS DRIVES EPITHELIAL REGENERATION FROM PANETH CELL DEDIFFERENTIATION Open
NOT PUBLISHED AT AUTHOR’S REQUEST Please acknowledge all funding agencies listed below Funding Agencies CCC, CIHR
View article: GSDMD pore formation regulates caspase-4 cleavage to limit IL-18 production in the intestinal epithelium
GSDMD pore formation regulates caspase-4 cleavage to limit IL-18 production in the intestinal epithelium Open
Epithelial inflammasomes induce pyroptosis and release cytokines to defend against cytosolic pathogens. However, pyroptosis in epithelial barriers must be carefully regulated to facilitate elimination of infected cells while limiting wides…
View article: Bacterial ADP-heptose initiates a revival stem cell program in the intestinal epithelium
Bacterial ADP-heptose initiates a revival stem cell program in the intestinal epithelium Open
The intestinal epithelium has an exceptional capacity to repair following injury, and recent evidence has suggested that YAP-dependent signaling was crucial for the expansion of Clu + revival stem cells (revSCs) with fetal-like characteris…
View article: NLRX1 Prevents M2 Macrophage Polarization and Excessive Renal Fibrosis in Chronic Obstructive Nephropathy
NLRX1 Prevents M2 Macrophage Polarization and Excessive Renal Fibrosis in Chronic Obstructive Nephropathy Open
Background: Chronic kidney disease often leads to kidney dysfunction due to renal fibrosis, regardless of the initial cause of kidney damage. Macrophages are crucial players in the progression of renal fibrosis as they stimulate inflammati…
View article: NLRX1: Versatile functions of a mitochondrial NLR protein that controls mitophagy
NLRX1: Versatile functions of a mitochondrial NLR protein that controls mitophagy Open
NLRX1 is a member of the of the Nod-like receptor (NLR) family, and it represents a unique pattern recognition molecule (PRM) as it localizes to the mitochondrial matrix in resting conditions. Over the past fifteen years, NLRX1 has been pr…
View article: A178 ELUCIDATING THE ROLE OF THE LEUCINE-RICH REPEAT KINASE 2 G2019S MUTATION IN CROHN’S DISEASE PATHOGENESIS USING A CITROBACTER RODENTIUM INFECTIOUS COLITIS MODEL
A178 ELUCIDATING THE ROLE OF THE LEUCINE-RICH REPEAT KINASE 2 G2019S MUTATION IN CROHN’S DISEASE PATHOGENESIS USING A CITROBACTER RODENTIUM INFECTIOUS COLITIS MODEL Open
Background Associations have been found linking certain LRRK2 kinase domain gain-of-function variants, such as G2019S, to the development of Crohn’s disease and Parkinson’s disease, yet their exact roles in pathogenesis remains elusive. LR…
View article: A22 USING INTESTINAL ORGANOIDS TO CHARACTERIZE THE NAIP-NLRC4 INFLAMMASOME RESPONSE IN THE INTESTINAL EPITHELIUM
A22 USING INTESTINAL ORGANOIDS TO CHARACTERIZE THE NAIP-NLRC4 INFLAMMASOME RESPONSE IN THE INTESTINAL EPITHELIUM Open
Background The NAIP-NLRC4 inflammasome is an important innate defence mechanism in intestinal epithelial cells (IECs) that protects the gut from invasive pathogens. NAIP-NLRC4 activation triggers pyroptotic cell death, releases active inte…
View article: Cytosolic retention of the mitochondrial protease HtrA2 during mitochondrial protein import stress (MPIS) triggers the DELE1-HRI pathway
Cytosolic retention of the mitochondrial protease HtrA2 during mitochondrial protein import stress (MPIS) triggers the DELE1-HRI pathway Open
Mitochondrial stress inducers, such as the proton ionophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and the ATPase pump inhibitor oligomycin, trigger the DELE1-HRI branch of the integrated stress response (ISR) pathway. Previous s…
View article: Mitochondria-ER cooperation: NLRX1 detects mitochondrial protein import stress and promotes mitophagy through the ER protein RRBP1
Mitochondria-ER cooperation: NLRX1 detects mitochondrial protein import stress and promotes mitophagy through the ER protein RRBP1 Open
Mitochondria rely on efficient protein import across their membranes for optimal function. We have shown that numerous mitochondrial stressors all converge on a common pathway disrupting this import efficiency. We identified a novel pathwa…
View article: Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity
Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity Open
During obesity and high fat-diet (HFD) feeding in mice, sustained low-grade inflammation includes not only increased pro-inflammatory macrophages in the expanding adipose tissue, but also bone marrow (BM) production of invasive Ly6C high m…
View article: Invading Bacterial Pathogens Activate Transcription Factor EB in Epithelial Cells through the Amino Acid Starvation Pathway of mTORC1 Inhibition
Invading Bacterial Pathogens Activate Transcription Factor EB in Epithelial Cells through the Amino Acid Starvation Pathway of mTORC1 Inhibition Open
Upon pathogen infection, intricate innate signaling cascades are induced to initiate the transcription of immune effectors, including cytokines and chemokines. Transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and …
View article: A single cell survey of the microbial impacts on the mouse small intestinal epithelium
A single cell survey of the microbial impacts on the mouse small intestinal epithelium Open
The small intestinal epithelial barrier inputs signals from the gut microbiota in order to balance physiological inflammation and tolerance, and to promote homeostasis. Understanding the dynamic relationship between microbes and intestinal…
View article: Author response: Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity
Author response: Bone marrow adipocytes drive the development of tissue invasive Ly6Chigh monocytes during obesity Open
Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract During obesity and hig…
View article: NLRP1B and NLRP3 Control the Host Response following Colonization with the Commensal Protist <i>Tritrichomonas musculis</i>
NLRP1B and NLRP3 Control the Host Response following Colonization with the Commensal Protist <i>Tritrichomonas musculis</i> Open
Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on the host’s intestinal immune homeostasis, typically by elevating anti-microbia…
View article: NLRP1B and NLRP3 control the host response following colonization with the commensal protist <i>Tritrichomonas musculis</i>
NLRP1B and NLRP3 control the host response following colonization with the commensal protist <i>Tritrichomonas musculis</i> Open
Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on the host’s intestinal immune homeostasis, typically by elevating anti-microbia…
View article: How autophagy controls the intestinal epithelial barrier
How autophagy controls the intestinal epithelial barrier Open
Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal…
View article: Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells
Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells Open
Pioneering studies from the early 1980s suggested that bacterial peptidoglycan-derived muramyl peptides (MPs) could exert either stimulatory or immunosuppressive functions depending, in part, on chronicity of exposure. However, this Janus-…
View article: Tissue-selective alternate promoters guide NLRP6 expression
Tissue-selective alternate promoters guide NLRP6 expression Open
The pryin domain (PYD) domain is involved in protein interactions that lead to assembly of immune-sensing complexes such as inflammasomes. The repertoire of PYD-containing genes expressed by a cell type arms tissues with responses against …