scholarly journals Biological Functions of Interleukin-21 and Its Role in Inflammation

2007 ◽  
Vol 7 ◽  
pp. 1715-1735 ◽  
Author(s):  
Martin Pelletier ◽  
Denis Girard
Keyword(s):  
Potential Role ◽  
Inflammatory Diseases ◽  
Antitumor Agent ◽  
Biological Functions ◽  
Key Factor ◽  
Autoimmune And Inflammatory Diseases ◽  
Activated T Lymphocytes ◽  
Inflammatory Bowel ◽  
Interleukin 21 ◽  
Therapeutic Tools

Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, is mainly produced by activated T lymphocytes, particularly the inflammatory Th17subset, and is believed to be a key factor in the transition between innate and acquired immunity. In the last few years, this cytokine has been shown to modulate the functions of T, B, and NK cells, as well as cells of myeloid origin. In addition, it was demonstrated that IL-21 is a potent antitumor agent, making it a promising candidate for the development of therapeutic tools. IL-21 has also been associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. This review will summarize the biological functions of IL-21 and its potential role in inflammation.

scholarly journals Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

2017 ◽  
Vol 23 (33) ◽  
pp. 6137-6146 ◽  
Author(s):  
Morten L Halling ◽  
Jens Kjeldsen ◽  
Torben Knudsen ◽  
Jan Nielsen ◽  
Lars Koch Hansen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Increased Risk ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel

scholarly journals Faecalibacterium prausnitzii: A Next-Generation Probiotic in Gut Disease Improvement

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xiaoya He ◽  
Shuyang Zhao ◽  
Yan Li
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Inflammatory Diseases ◽  
Symbiotic Bacterium ◽  
Fecal Microbiota ◽  
Next Generation ◽  
Faecalibacterium Prausnitzii ◽  
Inflammatory Bowel ◽  
Therapeutic Tools ◽  
Culture Strategy

The researchers are paying more attention to the role of gut commensal bacteria in health development beyond the classical pathogens. It has been widely demonstrated that dysbiosis, which means the alternations of the gut microbial structure, is closely associated with development of intestinal chronic inflammation-related diseases such as inflammatory bowel disease (IBD), and even infectious diseases including bacterial and viral infection. Thus, for reshaping ecological balance, a growing body of the literatures have proposed numerous strategies to modulate the structure of the gut microbiota, which provide more revelation for amelioration of these inflammation or infection-related diseases. While the ameliorative effects of traditional probiotics seem negligeable, emerging next generation probiotics (NGPs) start to receive great attention as new preventive and therapeutic tools. Encouragingly, within the last decade, the intestinal symbiotic bacterium Faecalibacterium prausnitzii has emerged as the “sentinel of the gut,” with multifunction of anti-inflammation, gut barrier enhancement, and butyrate production. A lower abundance of F. prausnitzii has been shown in IBD, Clostridium difficile infection (CDI), and virus infection such as COVID-19. It is reported that intervention with higher richness of F. prausnitzii through dietary modulation, fecal microbiota transplantation, or culture strategy can protect the mice or the subjects from inflammatory diseases. Therefore, F. prausnitzii may have potential ability to reduce microbial translocation and inflammation, preventing occurrences of gastrointestinal comorbidities especially in COVID-19 patients.

scholarly journals Shared development of targeted therapies among autoimmune and inflammatory diseases: a systematic repurposing analysis

2020 ◽  
Vol 12 ◽  
pp. 1759720X2096926
Author(s):  
Arthur Petitdemange ◽  
Julien Blaess ◽  
Jean Sibilia ◽  
Renaud Felten ◽  
Laurent Arnaud
Keyword(s):  
Clinical Trials ◽  
Targeted Therapies ◽  
Lupus Erythematosus ◽  
Inflammatory Diseases ◽  
Drug Repurposing ◽  
Type I ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel

Background: Pathogenic inflammatory pathways are largely shared between different autoimmune and inflammatory diseases (AIDs). This offers the potential to develop a given targeted therapy in several AIDs. Methods: We analyzed two clinical trials registries (ClinicalTrials.gov and EU Clinical Trials Register) to identify the targeted therapies whose development is shared between at least two of the most common AIDs [rheumatoid arthritis (RA), spondyloarthritis (SpA), cutaneous psoriasis (cPso), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), giant cell arteritis (GCA), and multiple sclerosis (MS)] using an in-depth repurposing analysis. Results: We identified 142 shared targeted therapies. The four diseases in which shared targeted therapies were the most numerous were RA ( n = 92), cPso ( n = 67), IBD ( n = 58), and SLE ( n = 56). The two clusters of diseases between which the overlap of targeted therapies was the most important were RA and SLE as well as RA, SpA, cPso, and IBD. The targeted therapies which were shared by five diseases or more were abatacept, ustekinumab, rituximab, anakinra, etanercept, infliximab, secukinumab, tofacitinib, alemtuzumab, tocilizumab, adalimumab, apremilast, baricitinib, belimumab, brodalumab, filgotinib, and upadacitinib. The most frequently targeted molecules and pathways were (by descending frequency): JAK-STAT pathways, Th17 axis, TNF-α, IL-6, costimulation molecules, BAFF, CD20, BTK, chemokines and integrins, IL-1, and type I interferon. Conclusion: Many targeted therapies are developed in several AIDs, reflecting the overlap of pathogenic pathways and potential of drug repurposing. This suggests that a revision of the current, clinically based classification of AIDs towards a more mechanistic-based taxonomy might be relevant.

scholarly journals The Potential Role of Phytonutrients Flavonoids Influencing Gut Microbiota in the Prophylaxis and Treatment of Inflammatory Bowel Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Lina Wang ◽  
Mengxue Gao ◽  
Guangbo Kang ◽  
He Huang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Potential Role ◽  
Inflammatory Diseases ◽  
Symbiotic Relationship ◽  
Anti Oxidant ◽  
Inflammatory Bowel ◽  
Mammalian Intestine

Inflammatory bowel disease (IBD), characterized by the chronic inflammation of the gastrointestinal tract, is comprised of two idiopathic chronic intestinal inflammatory diseases. As the incidence of IBD increases, so does the need for safe and effective treatments. Trillions of microorganisms are colonized in the mammalian intestine, coevolve with the host in a symbiotic relationship. Gut microbiota has been reported to be involved in the pathophysiology of IBD. In this regard, phytonutrients flavonoids have received increasing attention for their anti-oxidant and anti-inflammatory activities. In this review, we address recent advances in the interactions among flavonoids, gut microbiota, and IBD. Moreover, their possible potential mechanisms of action in IBD have been discussed. We conclude that there is a complex interaction between flavonoids and gut microbiota. It is expected that flavonoids can change or reshape the gut microbiota to provide important considerations for developing treatments for IBD.

Clinical Application of Thiopurine Pharmacogenomics in Pediatrics

2020 ◽  
Vol 21 (1) ◽  
pp. 53-62
Author(s):  
Sonja Pavlovic ◽  
Nikola Kotur ◽  
Biljana Stankovic ◽  
Vladimir Gasic ◽  
Marianna Lucafo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Lymphoblastic Leukemia ◽  
Pediatric Care ◽  
Patient Treatment ◽  
Acute Leukemias ◽  
Treatment Protocols ◽  
Non Hodgkin Lymphoma ◽  
Pediatric Diseases ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel

Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.

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 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.

TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases

Immunotherapy ◽  
2021 ◽  
Author(s):  
Maciej Gonciarz ◽  
Katarzyna Pawlak-Buś ◽  
Piotr Leszczyński ◽  
Witold Owczarek
Keyword(s):  
Lupus Erythematosus ◽  
Tyrosine Kinases ◽  
Inflammatory Diseases ◽  
Cellular Responses ◽  
Protein Tyrosine Kinases ◽  
Type I Interferons ◽  
Type I ◽  
Intracellular Protein ◽  
Autoimmune And Inflammatory Diseases ◽  
Inflammatory Bowel

JAKs are intracellular protein tyrosine kinases that, through activation of STATs, are responsible for signal transduction pathways that regulate cellular responses to numerous cytokines, growth factors and hormones in many different cells. JAK-STAT signaling plays a key role in regulating immune function, and cytokines – such as IL-23, IL-12 and type I interferons – are central to the pathogenesis of autoimmune diseases, including psoriasis, inflammatory bowel disease and systemic lupus erythematosus. Here the authors review the evidence for targeting TYK2 as a more specific approach to treating these conditions. TYK2 inhibitors are clinically effective in autoimmune and inflammatory diseases and may avoid some of the complications reported with nonselective JAK inhibitors.

scholarly journals EFSUMB Recommendations for Gastrointestinal Ultrasound Part 3: Endorectal, Endoanal and Perineal Ultrasound

2019 ◽  
Vol 05 (01) ◽  
pp. E34-E51 ◽  
Author(s):  
Dieter Nuernberg ◽  
Adrian Saftoiu ◽  
Ana Barreiros ◽  
Eike Burmester ◽  
Elena Ivan ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Perineal Ultrasound ◽  
Therapy Planning ◽  
Contrast Enhanced Ultrasound ◽  
Rectal Tumors ◽  
Targeted Biopsy ◽  
Contrast Enhanced ◽  
Gastrointestinal Ultrasound ◽  
Examination Techniques ◽  
Inflammatory Bowel

AbstractThis article represents part 3 of the EFSUMB Recommendations and Guidelines for Gastrointestinal Ultrasound (GIUS). It provides an overview of the examination techniques recommended by experts in the field of endorectal/endoanal ultrasound (ERUS/EAUS), as well as perineal ultrasound (PNUS). The most important indications are rectal tumors and inflammatory diseases like fistula and abscesses in patients with or without inflammatory bowel disease (IBD). PNUS sometimes is more flexible and convenient compared to ERUS. However, the technique of ERUS is quite well established, especially for the staging of rectal cancer. EAUS also gained ground in the evaluation of perianal diseases like fistulas, abscesses and incontinence. For the staging of perirectal tumors, the use of PNUS in addition to conventional ERUS could be recommended. For the staging of anal carcinomas, PNUS can be a good option because of the higher resolution. Both ERUS and PNUS are considered excellent guidance methods for invasive interventions, such as the drainage of fluids or targeted biopsy of tissue lesions. For abscess detection and evaluation, contrast-enhanced ultrasound (CEUS) also helps in therapy planning.

scholarly journals A family harboring an MLKL loss of function variant implicates impaired necroptosis in diabetes

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Joanne M. Hildebrand ◽  
Bernice Lo ◽  
Sara Tomei ◽  
Valentina Mattei ◽  
Samuel N. Young ◽  
...  
Keyword(s):  
Potential Role ◽  
Autosomal Dominant ◽  
Inflammatory Diseases ◽  
Diabetic Patients ◽  
Incomplete Penetrance ◽  
Loss Of Function ◽  
Healthy Sibling ◽  
Dominant Disease ◽  
Terminal Effector

AbstractMaturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL−/− human cell lines. This MLKL mutation may act as a modifier to the P33T PDX1 mutation, and points to a potential role of impairment of necroptosis in diabetes. Our findings highlight the importance of family studies in unraveling MODY’s incomplete penetrance, and provide further support for the involvement of dysregulated necroptosis in human disease.

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