Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease

Friedrich, Matthias; Pohin, Mathilde; Powrie, Fiona

doi:10.1016/j.immuni.2019.03.017

Cited by 558 publications

(489 citation statements)

References 181 publications

(245 reference statements)

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“…Several interleukins are now targeted for IBD therapy [143] but with inconsistent efficacy [144], suggesting the importance of immuno-proteomic profiling in IBD patients. It is becoming clear that there is a complex network of cytokine production/activation in the inflamed bowel [145] which, in turn, is affected by its interplay with the microbial communities, host genetics, and environmental factors.…”

Section: Immuno-proteomics In Ibd Pathogenesismentioning

confidence: 99%

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

2019

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Background: Inflammatory Bowel Disease (IBD) is a multifactorial chronic disease. Understanding only one aspect of IBD pathogenesis does not reflect the complex nature of IBD nor will it improve its clinical management. Therefore, it is vital to dissect the interactions between the different players in IBD pathogenesis in order to understand the biology of the disease and enhance its clinical outcomes. Aims:To provide an overview of the available omics data used to assess the potential mechanisms through which various players are contributing to IBD pathogenesis and propose a precision medicine model to fill the current knowledge gap in IBD.Results: Several studies have reported microbial dysbiosis, immune and metabolic dysregulation in IBD patients, however, this data is not sufficient to create signatures that can differentiate between the disease subtypes or between disease relapse and remission. Conclusions:We summarized the current knowledge in the application of omics in IBD patients, and we showed that the current knowledge gap in IBD hinders the improvements of clinical decision for treatment as well as the prediction of disease relapse. We propose one way to fill this gap by implementing integrative analysis of various omics datasets generated from one patient at a single time point.

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Section: Immuno-proteomics In Ibd Pathogenesismentioning

confidence: 99%

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

2019

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“…The onset and pathophysiology of IBD are not fully understood, but the current concept is that uncontrolled immune reactivity against intestinal microorganisms combined with environmental factors in genetically predisposed individuals underlie pathogenesis (5)(6)(7)(8)(9)(10). Infiltration of pro-inflammatory immune cells into the intestinal mucosa is induced; this releases cytokines and chemokines, creating a vicious circle and perpetuating tissue damage (11). Moreover, IBD is characterized by intestinal microbiota dysbiosis, with a reduction in both bacterial quantity and diversity (10,12,13).…”

Section: Introductionmentioning

confidence: 99%

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Caër

Wick

2020

Front. Immunol.

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Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex immune-mediated disease of the gastrointestinal tract that increases morbidity and negatively influences the quality of life. Intestinal mononuclear phagocytes (MNPs) have a crucial role in maintaining epithelial barrier integrity while controlling pathogen invasion by activating an appropriate immune response. However, in genetically predisposed individuals, uncontrolled immune activation to intestinal flora is thought to underlie the chronic mucosal inflammation that can ultimately result in IBD. Thus, MNPs are involved in fine-tuning mucosal immune system responsiveness and have a critical role in maintaining homeostasis or, potentially, the emergence of IBD. MNPs include monocytes, macrophages and dendritic cells, which are functionally diverse but highly complementary. Despite their crucial role in maintaining intestinal homeostasis, specific functions of human MNP subsets are poorly understood, especially during diseases such as IBD. Here we review the current understanding of MNP ontogeny, as well as the recently identified human intestinal MNP subsets, and discuss their role in health and IBD.

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“…The imbalance between oxidative stress and antioxidant defense in patients with inflammatory bowel disease (IBD) has been well documented. 1 Production of oxidants and free radicals can facilitate the activation of signaling events that mediate the expression of inflammatory genes, as well as genes regulating cell division, differentiation, and apoptosis. 2,3 A surplus production of oxidative molecules can induce inflammation, injury, and death in intestinal epithelial cells (IECs) and cause mucosal barrier dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Glutathione S‐transferase theta 1 protects against colitis through goblet cell differentiation via interleukin‐22

et al. 2020

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The enzyme glutathione S‐transferase theta 1 (GSTT1) is involved in detoxifying chemicals, including reactive oxygen species (ROS). Here, we provide a significant insight into the role of GSTT1 in inflammatory bowel disease (IBD). We identified decreased expression of GSTT1 in inflamed colons from IBD patients compared to controls. We intrarectally or intraperitoneally delivered Gstt1 gene to mice with dextran sodium sulfate (DSS)‐induced colitis and noted attenuation of colitis through gene transfer of Gstt1 via an IL‐22 dependent pathway. Downregulation of GSTT1 by pathogen‐associated molecular patterns (PAMPs) of microbes reduced innate defense responses and goblet cell differentiation. The GSTT1 mutation in intestinal epithelial cells (IECs) and IBD patients decreased its dimerization, which was connected to insufficient phosphorylation of signal transducer and activator of transcription‐3 and p38/mitogen‐activated protein kinase by their common activator, IL‐22. GSTT1 ameliorated colitis and contributed as a modulator of goblet cells through sensing pathogens and host immune responses. Its mutations are linked to chronic intestinal inflammation due to its insufficient dimerization. Our results provide new insights into GSTT1 mutations that are linked to chronic intestinal inflammation due to its insufficient dimerization and their functional consequences in IBDs.

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Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease

Cited by 558 publications

References 181 publications

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Glutathione S‐transferase theta 1 protects against colitis through goblet cell differentiation via interleukin‐22

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