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 Tissue–Resident Memory T Cells in Chronic Inflammation—Local Cells with Systemic Effects?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 409
Author(s):  
Anoushka Ashok Kumar Samat ◽  
Jolijn van der Geest ◽  
Sebastiaan J. Vastert ◽  
Jorg van Loosdregt ◽  
Femke van Wijk
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Chronic Inflammation ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Chronic Inflammatory Diseases ◽  
Recent Developments ◽  
Resident Memory T Cells ◽  
Barrier Tissues

Chronic inflammatory diseases such as rheumatoid arthritis (RA), Juvenile Idiopathic Arthritis (JIA), psoriasis, and inflammatory bowel disease (IBD) are characterized by systemic as well as local tissue inflammation, often with a relapsing-remitting course. Tissue–resident memory T cells (TRM) enter non-lymphoid tissue (NLT) as part of the anamnestic immune response, especially in barrier tissues, and have been proposed to fuel chronic inflammation. TRM display a distinct gene expression profile, including upregulation of CD69 and downregulation of CD62L, CCR7, and S1PR1. However, not all TRM are consistent with this profile, and it is now more evident that the TRM compartment comprises a heterogeneous population, with differences in their function and activation state. Interestingly, the paradigm of TRM remaining resident in NLT has also been challenged. T cells with TRM characteristics were identified in both lymph and circulation in murine and human studies, displaying similarities with circulating memory T cells. This suggests that re-activated TRM are capable of retrograde migration from NLT via differential gene expression, mediating tissue egress and circulation. Circulating ‘ex-TRM’ retain a propensity for return to NLT, especially to their tissue of origin. Additionally, memory T cells with TRM characteristics have been identified in blood from patients with chronic inflammatory disease, leading to the hypothesis that TRM egress from inflamed tissue as well. The presence of TRM in both tissue and circulation has important implications for the development of novel therapies targeting chronic inflammation, and circulating ‘ex-TRM’ may provide a vital diagnostic tool in the form of biomarkers. This review elaborates on the recent developments in the field of TRM in the context of chronic inflammatory diseases.

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 Cytokines and Transgenic Matrix in Autoimmune Diseases: Similarities and Differences

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 559
Author(s):  
Ludmiła Szewczak ◽  
Katarzyna Donskow-Łysoniewska
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Inflammatory Diseases ◽  
Special Focus ◽  
Preclinical Models ◽  
Systemic Lupus ◽  
Chronic Inflammatory Diseases ◽  
Organ Specific ◽  
Disease Entities ◽  
Similarities And Differences

Autoimmune diseases are increasingly recognized as disease entities in which dysregulated cytokines contribute to tissue-specific inflammation. In organ-specific and multiorgan autoimmune diseases, the cytokine profiles show some similarities. Despite these similarities, the cytokines have different roles in the pathogenesis of different diseases. Altered levels or action of cytokines can result from changes in cell signaling. This article describes alterations in the JAK-STAT, TGF-β and NF-κB signaling pathways, which are involved in the pathogenesis of multiple sclerosis and systemic lupus erythematosus. There is a special focus on T cells in preclinical models and in patients afflicted with these chronic inflammatory diseases.

scholarly journals Lipid, fatty acid, carnitine- and choline derivative profiles in rheumatoid arthritis outpatients with different degrees of periodontal inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kathrin Beyer ◽  
Stein Atle Lie ◽  
Bodil Bjørndal ◽  
Rolf K. Berge ◽  
Asbjørn Svardal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Inflammatory Diseases ◽  
Whole Body ◽  
Cross Sectional ◽  
Chronic Inflammatory Diseases ◽  
Periodontal Inflammation ◽  
Inflammatory Status ◽  
Lipid Fatty Acid

AbstractRheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases with several pathogenic pathways in common. Evidence supports an association between the diseases, but the exact underlying mechanisms behind the connection are still under investigation. Lipid, fatty acid (FA) and metabolic profile alterations have been associated with several chronic inflammatory diseases, including RA and periodontitis. Mitochondria have a central role in regulating cellular bioenergetic and whole-body metabolic homeostasis, and mitochondrial dysfunction has been proposed as a possible link between the two disorders. The aim of this cross-sectional study was to explore whole-blood FA, serum lipid composition, and carnitine- and choline derivatives in 78 RA outpatients with different degrees of periodontal inflammation. The main findings were alterations in lipid, FA, and carnitine- and choline derivative profiles. More specifically, higher total FA and total cholesterol concentrations were found in active RA. Elevated phospholipid concentrations with concomitant lower choline, elevated medium-chain acylcarnitines (MC-AC), and decreased ratios of MC-AC and long-chain (LC)-AC were associated with prednisolone medication. This may indicate an altered mitochondrial function in relation to the increased inflammatory status in RA disease. Our findings may support the need for interdisciplinary collaboration within the field of medicine and dentistry in patient stratification to improve personalized treatment. Longitudinal studies should be conducted to further assess the potential impact of mitochondrial dysfunction on RA and periodontitis.

scholarly journals Immunopathogenesis and Treatment of Rheumatoid Arthritis: Recent Developments

2015 ◽  
Vol 7 (2) ◽  
pp. 62-67
Author(s):  
ASM Giasuddin ◽  
KA Jhuma ◽  
AMM Haq ◽  
MM Haque
Keyword(s):  
Rheumatoid Arthritis ◽  
Adult Population ◽  
Chronic Inflammatory Disease ◽  
Age Group ◽  
T Helper ◽  
T Helper Lymphocytes ◽  
Th17 Lymphocytes ◽  
Recent Developments ◽  
Cytokine Cascade

Rheumatoid arthritis (RA) is a chronic inflammatory disease occurring three times more in females throughout the world affecting 1-2% of the adult population in all ethnic groups, usually in the age group of 25-60 years. Although the role of CD4 + T helper lymphocytes in the aetiopathogenesis has been studied for more than three decades, the focus on CD4 + T helper type 17 (Th17) lymphocytes and its associated cytokines is much more recent. The cytokines such as IL-17 and IFN-g induce secondary cytokines such as IL-1, TNF-a , etc which possibly cause inflammation in joints. This cytokine cascade, therefore, offers a number of points and opportunities for immunointervention in RA. The present review article highlights some of the major aspects of the immunopathogenesis that involve Th17 cells and their association relevant to recent developments in the treatment of RA. DOI: http://dx.doi.org/10.3329/bjmb.v7i2.22415 Bangladesh J Med Biochem 2014; 7(2): 62-67

scholarly journals Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amritpal Dhaliwal ◽  
Felicity R. Williams ◽  
Jonathan I. Quinlan ◽  
Sophie L. Allen ◽  
Carolyn Greig ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Inflammatory Disease ◽  
Prospective Cohort ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Assessment Model ◽  
Chronic Inflammatory Diseases ◽  
Link Type ◽  
Disease Specific

Abstract Background Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, function and mass) and negatively impact on both morbidity and mortality. There is currently limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease-specific mechanisms driving sarcopenia. Therefore, this study aims to identify potential mechanisms driving sarcopenia within chronic inflammatory disease via a multi-modal approach; in an attempt to help define potential interventions for future use. Methods This prospective cohort study will consist of a multi-modal assessment of sarcopenia and its underlying mechanisms. Recruitment will target three chronic inflammatory diseases: chronic liver disease (CLD) (n=50), with a subset of NAFLD (n=20), inflammatory bowel disease (IBD) (n=50) and rheumatoid arthritis (RA) (n=50) both before and after therapeutic intervention. In addition, 20 age and sex matched healthy individuals will be recruited for comparison. Participants will undergo 4 assessment visits at weeks 0, 2, 12 and 24. Visits will consist of the following assessments: blood tests, anthropometrics, functional assessment, quadriceps muscle imaging, actigraphy, quality of life questionnaires, food diary collection and muscle biopsy of the vastus lateralis (at weeks 2 and 24 only). In addition, stool and urine samples will be collected for future microbiome and metabolomics analysis. Discussion This is the first study to use a multi-modal assessment model to phenotype sarcopenia in these chronic inflammatory diseases. We hope to identify generic as well as disease-specific mechanisms driving sarcopenia. We appreciate that these cohorts do require separate standards of care treatments which limit comparison between groups. Ethics and dissemination The study is approved by the Health Research Authority - West Midlands Solihull Research Ethics Service Committee Authority (REC reference: 18/WM/0167). Recruitment commenced in January 2019 and will continue until July 2021. The study was halted in March 2020 and again in January 2021 with the COVID-19 pandemic. The findings will be disseminated through peer-reviewed publications and conference presentations. All data will be stored on a secure server. Trial registration ClinicalTrials.gov Identifier: NCT04734496

scholarly journals Blood Immunoproteasome Activity Is Regulated by Sex, Age and in Chronic Inflammatory Diseases: A First Population-Based Study

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3336
Author(s):  
Ilona Elisabeth Kammerl ◽  
Claudia Flexeder ◽  
Stefan Karrasch ◽  
Barbara Thorand ◽  
Margit Heier ◽  
...  
Keyword(s):  
Active Sites ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Population Based ◽  
Chronic Inflammatory Disease ◽  
Chronic Obstructive ◽  
Peripheral Blood Mononuclear ◽  
Chronic Inflammatory Diseases ◽  
Study Participants ◽  
The Impact

Dysfunction of the immunoproteasome has been implicated in cardiovascular and pulmonary diseases. Its potential as a biomarker for predicting disease stages, however, has not been investigated so far and population-based analyses on the impact of sex and age are missing. We here analyzed the activity of all six catalytic sites of the proteasome in isolated peripheral blood mononuclear cells obtained from 873 study participants of the KORA FF4 study using activity-based probes. The activity of the immuno- and standard proteasome correlated clearly with elevated leukocyte counts of study participants. Unexpectedly, we observed a strong sex dimorphism for proteasome activity with significantly lower immunoproteasome activity in women. In aging, almost all catalytic activities of the proteasome were activated in aged women while maintained upon aging in men. We also noted distinct sex-related activation patterns of standard and immunoproteasome active sites in chronic inflammatory diseases such as diabetes, cardiovascular diseases, asthma, or chronic obstructive pulmonary disease as determined by multiple linear regression modeling. Our data thus provides a conceptual framework for future analysis of immunoproteasome function as a bio-marker for chronic inflammatory disease development and progression.

scholarly journals Comparative analysis of various metrics of arterial compliance in the study of chronic inflammatory diseases

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.L Kerkhof ◽  
R.B Djorai ◽  
A Maslyanskiy ◽  
E Kolesova ◽  
A.O Konradi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Arterial Stiffness ◽  
Arterial Pressure ◽  
Inflammatory Diseases ◽  
Arterial Compliance ◽  
Poor Correlation ◽  
Funding Source ◽  
Chronic Inflammatory Diseases ◽  
The Impact

Abstract Introduction Arterial compliance (AC), known to depend on age and sex, may be severely compromised in chronic inflammatory diseases. Apart from the various definitions for arterial stiffness that are in vogue, their constituent components are often not unique. Purpose This study compares vascular stiffness measures in various inflammatory diseases and explores a more comprehensive description of vessel wall properties by also considering inherent associated companion metrics. Methods We retrospectively analyzed arterial pressure, ventricular volume by echocardiography (Vivid-7 ultrasound system), along with carotid–femoral pulse wave velocity (PWV, by SphygmoCor, Atcor). Pulse pressure (PP) equals systolic arterial pressure (SAP) minus diastolic arterial pressure (DAP). Effective arterial elastance (Ea) = 0.9 × SAP/SV where SV is stroke volume. AC=SV/PP (Figure 1A). The intrinsic companion (C) to any established difference-based metric is calculated on the basis of the squared mean, e.g., PPC2 = (SAP2 + DAP2). Clearly, AC depends on two differences, each having a companion. Results A total of 177 patients (age range 18 to 80 years, 49 males), characterized by inflammatory disease (51 scleroderma, 62 atherosclerosis, 35 ankylosing spondylitis, and 29 rheumatoid arthritis), yielded reduced levels of vacular compliance irrespective of the method selected. Regression analysis showed weak correlations between the various approaches (i.e., Ea, AC, PWV). Average values for AC are comparable for all 4 diagnostic groups. Ea (P<0.03) and PWV (P<0.014) are lower for ankylosing spondylitis compared to all other groups, likely due to younger age and the higher prevalence of men. Ea is highest in atherosclerosis (P<0.026) versus all other groups. SV is significantly higher in atherosclerosis (P<0.03) compared to scleroderma and rheumatoid arthritis. However, the companions may differ (Figure 1B): PPC is significantly (P=0.017) higher in atherosclerosis (156.3±16.1 mmHg) vs scleroderma (147.2±23.0 mmHg), while SVC in ankylosing spondylitis is higher (P<0.013) than in all other groups. Conclusions Arterial stiffness measures show poor correlation, suggesting limitations to their utility when studying the diagnostic groups described here. Consideration of the companion associated with each difference-based metric is warranted in order to perform a comprehensive analysis of clinical data when evaluating the impact on risk factors and prognosis. Figure 1. A: Compliance components. B: Companions Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Science Foundation

Sign in / Sign up

Export Citation Format

Share Document