scholarly journals The Role of TL1A and DR3 in Autoimmune and Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yoshihiro Aiba ◽  
Minoru Nakamura
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Biliary Cirrhosis ◽  
Tnf Superfamily ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel ◽  
Irritable Bowel

TNF-like ligand 1A (TL1A), which binds its cognate receptor DR3 and the decoy receptor DcR3, is an identified member of the TNF superfamily. TL1A exerts pleiotropic effects on cell proliferation, activation, and differentiation of immune cells, including helper T cells and regulatory T cells. TL1A and its two receptors expression is increased in both serum and inflamed tissues in autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Polymorphisms of theTNFSF15gene that encodes TL1A are associated with the pathogenesis of irritable bowel syndrome, leprosy, and autoimmune diseases, including IBD, AS, and primary biliary cirrhosis (PBC). In mice, blocking of TL1A-DR3 interaction by either antagonistic antibodies or deletion of the DR3 gene attenuates the severity of multiple autoimmune diseases, whereas sustained TL1A expression on T cells or dendritic cells induces IL-13-dependent small intestinal inflammation. This suggests that modulation of TL1A-DR3 interaction may be a potential therapeutic target in several autoimmune diseases, including IBD, RA, AS, and PBC.

scholarly journals Regulatory T cells in acute and chronic kidney diseases

2018 ◽  
Vol 314 (5) ◽  
pp. F679-F698 ◽  
Author(s):  
Rahul Sharma ◽  
Gilbert R. Kinsey
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Peripheral Tolerance ◽  
Autoimmune And Inflammatory Diseases

Foxp3-expressing CD4+ regulatory T cells (Tregs) make up one subset of the helper T cells (Th) and are one of the major mechanisms of peripheral tolerance. Tregs prevent abnormal activation of the immune system throughout the lifespan, thus protecting from autoimmune and inflammatory diseases. Recent studies have elucidated the role of Tregs beyond autoimmunity. Tregs play important functions in controlling not only innate and adaptive immune cell activation, but also regulate nonimmune cell function during insults and injury. Inflammation contributes to a multitude of acute and chronic diseases affecting the kidneys. This review examines the role of Tregs in pathogenesis of renal inflammatory diseases and explores the approaches for enhancing Tregs for prevention and therapy of renal inflammation.

XII. IL-10-deficient (IL-10−/−) mice and intestinal inflammation

2000 ◽  
Vol 278 (6) ◽  
pp. G829-G833 ◽  
Author(s):  
Donna M. Rennick ◽  
Madeline M. Fort
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Intestinal Inflammation ◽  
Intestinal Disease ◽  
Regulatory Cells ◽  
Experimental Animal Models ◽  
Inflammatory Bowel ◽  
Ifn Γ ◽  
Small And Large Intestine

Interleukin (IL)-10−/−mice spontaneously develop intestinal inflammation characterized by discontinuous transmural lesions affecting the small and large intestine and by dysregulated production of proinflammatory cytokines. The uncontrolled generation of IFN-γ-producing CD4+T cells (Th1 type) has been shown to play a causal role in the development of enterocolitis affecting these mutants. This article discusses studies of IL-10−/−mice that have investigated the role of enteric organisms in triggering intestinal disease, the mediators responsible for initiating and maintaining intestinal disease, the role IL-10 plays in the generation and/or function of regulatory cells, and the results of IL-10 therapy in experimental animal models of inflammatory bowel disease (IBD) and human patients with IBD.

TREX1 As a Potential Therapeutic Target for Autoimmune and Inflammatory Diseases

2019 ◽  
Vol 25 (30) ◽  
pp. 3239-3247 ◽  
Author(s):  
Sha-Sha Tao ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
Rui-Xue Leng ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Therapeutic Target ◽  
Mammalian Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Autoimmune Response ◽  
Autoimmune And Inflammatory Diseases ◽  
Functional Mechanisms

Background and Objectives: The 3’ repair exonuclease 1 (TREX1) gene is the major DNA-specific 3’–5 ’exonuclease of mammalian cells which reduces single- and double-stranded DNA (ssDNA and dsDNA) to prevent undue immune activation mediated by the nucleic acid. TREX1 is also a crucial suppressor of selfrecognition that protects the host from inappropriate autoimmune activations. It has been revealed that TREX1 function is necessary to prevent host DNA accumulating after cell death which could actuate an autoimmune response. In the manuscript, we will discuss in detail the latest advancement to study the role of TREX1 in autoimmune disease. Methods: As a pivotal cytoprotective, antioxidant, anti-apoptotic, immunosuppressive, as well as an antiinflammatory molecule, the functional mechanisms of TREX1 were multifactorial. In this review, we will briefly summarize the latest advancement in studying the role of TREX1 in autoimmune disease, and discuss its potential as a therapeutic target for these diseases. Results: Deficiency of TREX1 in human patients and murine models is characterized by systemic inflammation and the disorder of TREX1 functions drives inflammatory responses leading to autoimmune disease. Moreover, much more studies revealed that mutations in TREX1 have been associated with a range of autoimmune disorders. But it is also unclear whether the mutations of TREX1 play a causal role in the disease progression, and whether manipulation of TREX1 has a beneficial effect in the treatment of autoimmune diseases. Conclusion: Integration of functional TREX1 biology into autoimmune diseases may further deepen our understanding of the development and pathogenesis of autoimmune diseases and provide new clues and evidence for the treatment of autoimmune diseases.

scholarly journals CARD9 mediates dendritic cell–induced development of Lyn deficiency–associated autoimmune and inflammatory diseases

2019 ◽  
Vol 12 (602) ◽  
pp. eaao3829 ◽  
Author(s):  
Jun Ma ◽  
Clare L. Abram ◽  
Yongmei Hu ◽  
Clifford A. Lowell
Keyword(s):  
Dendritic Cell ◽  
Inflammatory Diseases ◽  
Adaptor Protein ◽  
Experimental Colitis ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel ◽  
Vital Component ◽  
Genetic Deletion ◽  
Specific Deletion

CARD9 is an immune adaptor protein in myeloid cells that is involved in C-type lectin signaling and antifungal immunity. CARD9 is implicated in autoimmune and inflammatory-related diseases, such as rheumatoid arthritis, IgA nephropathy, ankylosing spondylitis, and inflammatory bowel disease (IBD). Given that Lyn-deficient (Lyn−/−) mice are susceptible to both autoimmunity and IBD, we investigated the immunological role of CARD9 in the development of these diseases using the Lyn−/− mouse model. We found that genetic deletion of CARD9 was sufficient to reduce the development of both spontaneous autoimmune disease as well as DSS- or IL-10 deficiency–associated colitis in Lyn−/− mice. Mechanistically, CARD9 was a vital component of the Lyn-mediated regulation of Toll-like receptor (TLR2 and TLR4) signaling in dendritic cells, but not in macrophages. In the absence of Lyn, signaling through a CD11b-Syk-PKCδ-CARD9 pathway was amplified, leading to increased TLR-induced production of inflammatory cytokines. Dendritic cell–specific deletion of CARD9 reversed the development of autoimmune and experimental colitis observed in dendritic cell–specific, Lyn-deficient mice. These findings suggest that targeting CARD9 may suppress the development of colitis and autoimmunity by reducing dendritic cell–driven inflammation.

scholarly journals Extracellular DNA Correlates with Intestinal Inflammation in Chemically Induced Colitis in Mice

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 81
Author(s):  
Martin Maronek ◽  
Barbora Gromova ◽  
Robert Liptak ◽  
Barbora Konecna ◽  
Michal Pastorek ◽  
...  
Keyword(s):  
Disease Activity ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Relative Proportion ◽  
Extracellular Dna ◽  
Absolute Amount ◽  
Chemically Induced ◽  
Inflammatory Bowel ◽  
Severe Colitis

Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.

Are Viruses and Parasites Linked to Celiac Disease? A Question that Still has no Definite Answer

2019 ◽  
Vol 20 (14) ◽  
pp. 1181-1193 ◽  
Author(s):  
Aref Shariati ◽  
Hamid R. Aslani ◽  
Mohammad R.H. Shayesteh ◽  
Ali Taghipour ◽  
Ahmad Nasser ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Multiple Roles ◽  
Barr Virus ◽  
The People ◽  
Intestinal Infections ◽  
Inflammatory Bowel ◽  
Epstein Barr ◽  
Irritable Bowel ◽  
Related Proteins

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

scholarly journals The Role of Enterobacteriaceae in Gut Microbiota Dysbiosis in Inflammatory Bowel Diseases

2021 ◽  
Vol 9 (4) ◽  
pp. 697
Author(s):  
Valerio Baldelli ◽  
Franco Scaldaferri ◽  
Lorenza Putignani ◽  
Federica Del Chierico
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Diseases ◽  
Species Level ◽  
Unknown Etiology ◽  
Gut Dysbiosis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Symbiotic Microbiota ◽  
Gut Microbiota Dysbiosis

Inflammatory bowel diseases (IBDs) are a group of chronic gastrointestinal inflammatory diseases with unknown etiology. There is a combination of well documented factors in their pathogenesis, including intestinal microbiota dysbiosis. The symbiotic microbiota plays important functions in the host, and the loss of beneficial microbes could favor the expansion of microbial pathobionts. In particular, the bloom of potentially harmful Proteobacteria, especially Enterobacteriaceae, has been described as enhancing the inflammatory response, as observed in IBDs. Herein, we seek to investigate the contribution of Enterobacteriaceae to IBD pathogenesis whilst considering the continuous expansion of the literature and data. Despite the mechanism of their expansion still remaining unclear, their expansion could be correlated with the increase in nitrate and oxygen levels in the inflamed gut and with the bile acid dysmetabolism described in IBD patients. Furthermore, in several Enterobacteriaceae studies conducted at a species level, it has been suggested that some adherent-invasive Escherichia coli (AIEC) play an important role in IBD pathogenesis. Overall, this review highlights the pivotal role played by Enterobacteriaceae in gut dysbiosis associated with IBD pathogenesis and progression.

Obesity and inflammatory bowel disease

2021 ◽  
Vol 75 (1) ◽  
pp. 20-28
Author(s):  
Vladimír Teplan ◽  
Milan Lukáš
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adipose Tissue ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Perioperative Complications ◽  
Overweight And Obesity ◽  
Special Role ◽  
Low Concentrations ◽  
Inflammatory Bowel

The incidence and prevalence of overweight and obesity has dramatically increased in the last decades and is generally considered to be global pandemics. The incidence of inflammatory bowel disease (IBD) is rising parallel with overweight and obesity. Contrary to a conventional believe, about 15–40% patients with IBD are obese, which can contribute to the development and course of IBD, especially in Crohn’s disease. Although the findings of some cohort studies are still conflicting, recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue known as creeping fat, leading to intestinal inflammation. The involvement of altered adipocyte function and deregulated production of adipokines such as leptin and adiponectin has been suggested in the pathogenesis of IBD. The emerging role of Western diet and microbiota can also open new possibilities in IBD management. The effect of obesity on the IBD-related therapy remains to be studied. The finding that obesity results in suboptimal response to the therapy, potentially promoting rapid clearance of biologic agents and thus leading to their low concentrations, has a great importance. Obesity also makes IBD colorectal surgery technically challenging and might increase a risk of perioperative complications.

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