NOD2 drives early IL-33–dependent expansion of group 2 innate lymphoid cells during Crohn’s disease–like ileitis

Salvo, Carlo De; Buela, Kristine-Ann; Creyns, Brecht; Corridoni, Daniele; Rana, Nitish; Wargo, H; Cominelli, Chiara; Delaney, Peter G.; Rodriguez-Palacios, Alexander; Cominelli, Fabio; Vermeire, Séverine; Pizarro, Theresa T.

doi:10.1172/jci140624

Cited by 29 publications

(23 citation statements)

References 25 publications

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“…ILC2s participate in IBD through their ability to sense microbiota, be stimulated by cytokines and maintain the intestinal barrier. The early IL-33–dependent expansion of ILC2s in CD is driven by activation of the intracellular pattern recognition receptor NOD2, as evidenced in gut-derived ILC2s from CD patients [ 195 ] and SAMP1/YitFc (SAMP) mice, a mouse strain that spontaneously develops a progressive, chronic intestinal inflammation similar to CD (reviewed in [ 196 ]). NOD2 detects muramyl dipeptide, a peptidoglycan by-product found in cell walls of both gram-positive and gram-negative bacteria.…”

Section: Ilcs and Inflammatory Bowel Diseasementioning

confidence: 99%

Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

Saéz

Gómez-Bris

Herrero‐Fernández

et al. 2021

IJMS

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Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation of unknown cause encompassing Crohn’s disease (CD) and ulcerative colitis (UC). IBD has been linked to genetic and environmental factors, microbiota dysbiosis, exacerbated innate and adaptive immunity and epithelial intestinal barrier dysfunction. IBD is classically associated with gut accumulation of proinflammatory Th1 and Th17 cells accompanied by insufficient Treg numbers and Tr1 immune suppression. Inflammatory T cells guide innate cells to perpetuate a constant hypersensitivity to microbial antigens, tissue injury and chronic intestinal inflammation. Recent studies of intestinal mucosal homeostasis and IBD suggest involvement of innate lymphoid cells (ILCs). These lymphoid-origin cells are innate counterparts of T cells but lack the antigen receptors expressed on B and T cells. ILCs play important roles in the first line of antimicrobial defense and contribute to organ development, tissue protection and regeneration, and mucosal homeostasis by maintaining the balance between antipathogen immunity and commensal tolerance. Intestinal homeostasis requires strict regulation of the quantity and activity of local ILC subpopulations. Recent studies demonstrated that changes to ILCs during IBD contribute to disease development. A better understanding of ILC behavior in gastrointestinal homeostasis and inflammation will provide valuable insights into new approaches to IBD treatment. This review summarizes recent research into ILCs in intestinal homeostasis and the latest advances in the understanding of the role of ILCs in IBD, with particular emphasis on the interaction between microbiota and ILC populations and functions.

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Section: Ilcs and Inflammatory Bowel Diseasementioning

confidence: 99%

Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

Saéz

Gómez-Bris

Herrero‐Fernández

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…Support T cells, lymphoid tissue inducer (LTi) cells, DCs, ILCs by secreting IL-7, IL-15, IL-33 [ 1 , 80 – 82 ]…”

Section: Figurementioning

confidence: 99%

“…In the context of infectious diseases, three factors affecting immune cell epigenetic programming are: (i) direct infection; (ii) pathogen-associated molecular patterns from microorganisms; and (iii) cytokines [ 80 ]. Is FRC-mediated LN structural remodeling another factor regulating immune cell epigenetic programming?…”

Section: Figurementioning

confidence: 99%

Lymph node fibroblastic reticular cells steer immune responses

Abdi

et al. 2021

Trends in Immunology

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Lymph nodes (LNs), where immune responses are initiated, are organized into distinctive compartments by fibroblastic reticular cells (FRCs). FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. Recent high-resolution transcriptional and histological analyses have enriched our knowledge of LN FRC genetic and spatial heterogeneities. Here, we summarize updated anatomic, phenotypic, and functional identities of FRC subsets, delve into topological and transcriptional remodeling of FRCs in inflammation, and illustrate the crosstalk between FRCs and immune cells. Discussing FRC functions in immunity and tolerance, we highlight state-of-the-art FRC-based therapeutic approaches for maintaining physiological homeostasis, steering protective immunity, inducing transplantation tolerance, and treating diverse immune-related diseases.

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“…IL-12, IL-23, and TNF-α produced by macrophages or DCs drive chronic inflammation that characterizes CD by inducing Th1 and Th17 responses. IL-33 produced by myofibroblasts and epithelial cells has been shown to augment Th1 responses associated with CD ( Figure 1A ; Pastorelli et al, 2010 ; Bonilla et al, 2012 ; Sedhom et al, 2013 ; Baumann et al, 2015 ; De Salvo et al, 2021 ). Mice deficient in ST2 are resistant to trinitrobenzene sulfonic acid (TNBS)-induced colitis, an experimental model of CD ( Sedhom et al, 2013 ).…”

Section: Il-33 and Crohn’s Diseasementioning

confidence: 99%

“…IL-33 markedly increased profibrogenic Th2 responses in SAMP1/YitFc mice, which spontaneously develop CD-like ileitis ( Pastorelli et al, 2010 ). IL-33-dependent expansion of ILC2 cells producing IL-5 and IL-13 causes intestinal fibrosis in SAMP1/YitFc mice ( De Salvo et al, 2021 ). These studies suggest that IL-33 produced by epithelial cells and myofibroblasts promotes inflammation and fibrosis associated with Th1 and Th2 responses, respectively.…”

Section: Il-33 and Crohn’s Diseasementioning

confidence: 99%

IL-33 as a Critical Cytokine for Inflammation and Fibrosis in Inflammatory Bowel Diseases and Pancreatitis

et al. 2021

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IL-33 is a pleiotropic cytokine that promotes inflammation and fibrosis. IL-33 is produced by a broad range of cells, including antigen-presenting cells (APCs), epithelial cells, and fibroblasts. IL-33 produced by the innate immune cells has been shown to activate pro-inflammatory T helper type 1 (Th1) and T helper type 2 (Th2) responses. The intestinal barrier and tolerogenic immune responses against commensal microbiota contribute to the maintenance of gut immune homeostasis. Breakdown of tolerogenic responses against commensal microbiota as a result of intestinal barrier dysfunction underlies the immunopathogenesis of inflammatory bowel diseases (IBD) and pancreatitis. Recent studies have provided evidence that IL-33 is an innate immune cytokine that bridges adaptive Th1 and Th2 responses associated with IBD and pancreatitis. In this Mini Review, we discuss the pathogenic roles played by IL-33 in the development of IBD and pancreatitis and consider the potential of this cytokine to be a new therapeutic target.

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NOD2 drives early IL-33–dependent expansion of group 2 innate lymphoid cells during Crohn’s disease–like ileitis

Cited by 29 publications

References 25 publications

Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

Lymph node fibroblastic reticular cells steer immune responses

IL-33 as a Critical Cytokine for Inflammation and Fibrosis in Inflammatory Bowel Diseases and Pancreatitis

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