scholarly journals Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases

2021 ◽  
Author(s):  
Ilya Korsunsky ◽  
Kevin Wei ◽  
Mathilde Pohin ◽  
Edy Y. Kim ◽  
Francesca Barone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Single Cell ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Chronic Inflammatory Diseases ◽  
Single Cell Rna Sequencing ◽  
Inflammatory Bowel ◽  
Novel Therapeutic

SummaryPro-inflammatory fibroblasts are critical to pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren’s syndrome, and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited the understanding of which pathways are shared by multiple diseases. To investigate, we profiled patient-derived fibroblasts from inflamed and non-inflamed synovium, intestine, lung, and salivary glands with single-cell RNA-sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes. Two shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts were expanded in all inflamed tissues and additionally mapped to dermal analogues in a public atopic dermatitis atlas. We further confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation. This work represents the first cross-tissue, single-cell fibroblast atlas revealing shared pathogenic activation states across four chronic inflammatory diseases.

scholarly journals New Perspectives in the Study of Intestinal Inflammation: Focus on the Resolution of Inflammation

2021 ◽  
Vol 22 (5) ◽  
pp. 2605
Author(s):  
Miguel Camba-Gómez ◽  
Oreste Gualillo ◽  
Javier Conde-Aranda
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Point Of View ◽  
Induction Phase ◽  
Resolution Of Inflammation ◽  
Chronic Inflammatory Diseases ◽  
Inflammatory Bowel ◽  
Tissue Trauma

Inflammation is an essential physiological process that is directed to the protection of the organism against invading pathogens or tissue trauma. Most of the existing knowledge related to inflammation is focused on the factors and mechanisms that drive the induction phase of this process. However, since the recognition that the resolution of the inflammation is an active and tightly regulated process, increasing evidence has shown the relevance of this process for the development of chronic inflammatory diseases, such as inflammatory bowel disease. For that reason, with this review, we aimed to summarize the most recent and interesting information related to the resolution process in the context of intestinal inflammation. We discussed the advances in the understanding of the pro-resolution at intestine level, as well as the new mediators with pro-resolutive actions that could be interesting from a therapeutic point of view.

scholarly journals Effects of Anti-Cytokine Antibodies on Gut Barrier Function

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Fang Liu ◽  
Seul A. Lee ◽  
Stephen M. Riordan ◽  
Li Zhang ◽  
Lixin Zhu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Barrier Function ◽  
Inflammatory Diseases ◽  
Immunomodulatory Effects ◽  
Gut Barrier ◽  
Barrier Integrity ◽  
Chronic Inflammatory Diseases ◽  
Gut Barrier Function ◽  
Inflammatory Bowel

Anti-cytokine antibodies are used in treating chronic inflammatory diseases and autoimmune diseases such as inflammatory bowel disease and rheumatic diseases. Patients with these diseases often have a compromised gut barrier function, suggesting that anti-cytokine antibodies may contribute to the re-establishment of gut barrier integrity, in addition to their immunomodulatory effects. This paper reviews the effects of anti-cytokine antibodies on gut barrier function and their mechanisms.

scholarly journals Targeting interleukin-17 in chronic inflammatory disease: A clinical perspective

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Pascale Zwicky ◽  
Susanne Unger ◽  
Burkhard Becher
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Interleukin 17 ◽  
Clinical Perspective ◽  
Preclinical Models ◽  
Chronic Inflammatory Diseases ◽  
Recent Developments ◽  
Disease Entities ◽  
Barrier Tissues

Chronic inflammatory diseases like psoriasis, Crohn’s disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and others are increasingly recognized as disease entities, where dysregulated cytokines contribute substantially to tissue-specific inflammation. A dysregulation in the IL-23/IL-17 axis can lead to inflammation of barrier tissues, whereas its role in internal organ inflammation remains less clear. Here we discuss the most recent developments in targeting IL-17 for the treatment of chronic inflammation in preclinical models and in patients afflicted with chronic inflammatory diseases.

scholarly journals Proposed grading scheme for inflammatory bowel disease in ferrets and correlation with clinical signs

2019 ◽  
Vol 32 (1) ◽  
pp. 17-24
Author(s):  
Paola Cazzini ◽  
Megan K. Watson ◽  
Nicole Gottdenker ◽  
Joerg Mayer ◽  
Drury Reavill ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Utility ◽  
Intestinal Inflammation ◽  
Companion Animals ◽  
Clinical Signs ◽  
Chronic Inflammatory Disease ◽  
Mustela Putorius ◽  
Crypt Abscess ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is an idiopathic, chronic, inflammatory disease of the gastrointestinal tract of companion animals, including ferrets ( Mustela putorius furo). Clinical signs of IBD are nonspecific, and intestinal biopsies are necessary for a definitive diagnosis. A grading scheme has not been established for ferrets. Additionally, the association between histologic severity and clinical signs in ferrets is unknown. We evaluated enteric samples from ferrets diagnosed with IBD, compared histologic grading schemes, and correlated the results with the severity of clinical signs. Enteric sections from 23 ferrets with IBD were analyzed using grading schemes for intestinal inflammation in cats and dogs, and a correlation with clinical signs was evaluated. After dividing the histologic samples into groups based on the severity of clinical signs, main histologic differences were identified. Age and sex were also assessed for correlation with clinical signs. No significant correlation was found between the 2 grading schemes and clinical signs (rho = 0.02, p = 0.89; rho = 0.26, p = 0.18, respectively). Degree of villus fusion, hemorrhage and/or fibrin, epithelial damage, inflammation density, and crypt abscess formation were used retrospectively to create a ferret IBD grading scheme, which was significantly correlated with the severity of clinical signs (rho = 0.48, p = 0.01). A positive correlation was observed between age ( p = 0.04) and females ( p = 0.007) with severity of clinical signs. Our ferret grading scheme may have clinical utility in providing a more objective, consistent evaluation of IBD in ferrets.

Anti-Inflammatory Drugs

2006 ◽  
Author(s):  
Jie Jack Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Chronic Inflammatory Disease ◽  
Medical Society ◽  
Loss Of Function ◽  
Hard Time ◽  
Back Door ◽  
Inflammatory Bowel ◽  
William Osler

Inflammation and immunity, like all other normal reactions of the body, are meant to preserve or restore health. They can nonetheless cause a range of uncomfortable symptoms. Inflammation is such a complicated process that one would have a hard time reaching a consensus on its definition. Historically, inflammation was one of the earliest recognized and defined diseases. Two thousand years ago, Roman physician and encyclopedist Aulus Cornelius Celsus (25 B.C.–50 A.D., not to be confused with Celsius, the unit for temperature) described the four cardinal signs of inflammation: calor (warmth), dolor (pain), tumor (swelling), and rubor (redness). The fifth element of inflammation, functio laesi (loss of function or movement), was noted later. Classic inflammatory diseases include rheumatoid arthritis and Crohn’s disease, an inflammatory bowel disease. However, evidence is mounting that inflammation is implicated in many diseases that are not normally considered inflammatory. For instance, when arterial plaques become inflamed they can burst open, prompting a myriad of heart diseases. Inflammatory bowel conditions greatly increase the risk of colon tumors. Even diabetes has been associated with a number of inflammatory compounds. It was hard to define what inflammation was, but finding a remedy was even more challenging. Aspirin, available in 1880, represented possibly the first really effective treatment for inflammation, whereas cortisone and other corticosteroids were not available for the treatment of rheumatoid arthritis until the early 1950s. Louis Pasteur stated, “Dans les champs de l’observation, le hazard ne favorise que les esprit préparés” [In the field of experimentation, chance favors the prepared mind]. Like numerous cases in drug discovery, Philip S. Hench’s discovery of cortisone for the treatment of rheumatoid arthritis illustrates Pasteur’s point. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, swelling, and subsequent destruction of joints. Until the late 1940s, there was no viable treatment, and, understandably, pessimism prevailed in medical society about its prognosis. Even William Osler, one of the greatest physicians, said “When an arthritic patient walks in the front door, I want to run out the back door!” The situation did not change much until Hench discovered a “miracle drug” in 1949.

scholarly journals Glucocorticoid dose-dependent risk of type 2 diabetes in six immune-mediated inflammatory diseases: a population-based cohort analysis

2020 ◽  
Vol 8 (1) ◽  
pp. e001220
Author(s):  
Jianhua Wu ◽  
Sarah L Mackie ◽  
Mar Pujades-Rodriguez
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Population Based ◽  
Immune Mediated ◽  
Inflammatory Bowel ◽  
Dose Dependent

IntroductionIn immune-mediated inflammatory diseases, there is a lack of -estimates of glucocorticoid dose–response diabetes risk that consider changes in prescribed dose over time and disease activity.Research design and methodsPopulation-based longitudinal analysis of electronic health records from the UK Clinical Practice Research Datalink, linked to hospital admissions and the mortality registry (1998–2017). We included 100 722 adult patients without diabetes history, diagnosed with giant cell arteritis or polymyalgia rheumatica (n=32 593), inflammatory bowel disease (n=29 272), rheumatoid arthritis (n=28 365), vasculitis (n=6082), or systemic lupus erythematosus (n=4410). We estimated risks and HRs of type 2 diabetes associated with time-variant daily and total cumulative prednisolone-equivalent glucocorticoid dose using Cox regression methods.ResultsAverage patient age was 58.6 years, 65 469 (65.0%) were women and 8858 (22.6%) had a body mass index (BMI) ≥30 kg/m2. Overall, 8137 (8.1%) people developed type 2 diabetes after a median follow-up of 4.9 years. At 1 year, the cumulative risk of diabetes increased from 0.9% during periods of non-use to 5.0% when the daily prednisolone-equivalent dose was ≥25.0 mg. We found strong dose-dependent associations for all immune-mediated diseases, BMI levels and underlying disease duration, even after controlling for periods of active systemic inflammation. Adjusted HR for a <5.0 mg daily dose versus non-use was 1.90, 95% CI 1.44 to 2.50; range 1.70 for rheumatoid arthritis to 2.93 for inflammatory bowel disease.ConclusionsWe report dose-dependent risks of type 2 diabetes associated with glucocorticoid use for six common immune-mediated inflammatory diseases. These results underline the need for regular diabetic risk assessment and testing during glucocorticoid therapy in these patients.

Long term azathioprine fails to prevent onset of multiple sclerosis: report of two cases

2000 ◽  
Vol 6 (5) ◽  
pp. 362-363 ◽  
Author(s):  
C S Constantinescu ◽  
A Whiteley ◽  
L D Blumhardt
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Immunosuppressive Drug ◽  
Chronic Inflammatory Diseases ◽  
Definite Multiple Sclerosis ◽  
Clinically Definite Multiple Sclerosis ◽  
Inflammatory Bowel

Azathioprine is an immunosuppressive drug widely used in the treatment of chronic inflammatory diseases, including Multiple Sclerosis (MS). We report two patients who developed the first manifestations of clinically definite multiple sclerosis while on long term (3.5 and 10 years, respectively) treatment with azathioprine for Crohn's disease. Both patients developed the first MS symptoms during a quiescent phase of their inflammatory bowel disease. These cases show that long term azathioprine, while possibly maintaining inflammatory bowel disease under control, could not prevent the onset of MS.

Sign in / Sign up

Export Citation Format

Share Document