scholarly journals The Role of the IL-23/IL-17 Pathway in the Pathogenesis of Spondyloarthritis

2020 ◽  
Vol 21 (17) ◽  
pp. 6401 ◽  
Author(s):  
Hiroyuki Tsukazaki ◽  
Takashi Kaito
Keyword(s):  
Inflammatory Bowel Disease ◽  
Ankylosing Spondylitis ◽  
Mouse Models ◽  
Clinical Studies ◽  
Current Knowledge ◽  
Critical Role ◽  
Joint Inflammation ◽  
The Past ◽  
Inflammatory Bowel

Spondyloarthritis (SpA) is a subset of seronegative rheumatic-related autoimmune diseases that consist of ankylosing spondylitis (AS), psoriatic spondylitis (PsA), reactive spondylitis (re-SpA), inflammatory bowel disease (IBD)-associated spondylitis, and unclassifiable spondylitis. These subsets share clinical phenotypes such as joint inflammation and extra-articular manifestations (uveitis, IBD, and psoriasis [Ps]). Inflammation at the enthesis, where ligaments and tendons attach to bones, characterizes and distinguishes SpA from other types of arthritis. Over the past several years, genetic, experimental, and clinical studies have accumulated evidence showing that the IL-23/IL-17 axis plays a critical role in the pathogenesis of SpA. These discoveries include genetic association and the identification of IL-23- and IL-17-producing cells in the tissue of mouse models and human patients. In this review, we summarize the current knowledge of the pathomechanism by focusing on the IL-23/IL-17 pathway and examine the recent clinical studies of biological agents targeting IL-23 and IL-17 in the treatment of SpA.

scholarly journals Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhuo Xie ◽  
Mudan Zhang ◽  
Gaoshi Zhou ◽  
Lihui Lin ◽  
Jing Han ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Critical Role ◽  
Signalling Pathway ◽  
Hedgehog Signalling Pathway ◽  
Inflammatory Bowel ◽  
Effective Drugs

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

scholarly journals Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

2008 ◽  
Vol 105 (46) ◽  
pp. 17931-17936 ◽  
Author(s):  
Danyvid Olivares-Villagómez ◽  
Yanice V. Mendez-Fernandez ◽  
Vrajesh V. Parekh ◽  
Saif Lalani ◽  
Tiffaney L. Vincent ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Genetic Model ◽  
Critical Role ◽  
Intraepithelial Lymphocytes ◽  
Lymphocyte Function ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.

Slc26a3 (DRA) in the Gut: Expression, Function, Regulation, Role in Infectious Diarrhea and Inflammatory Bowel Disease

2020 ◽  
Author(s):  
Qin Yu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Current Knowledge ◽  
Cloning And Expression ◽  
Intestinal Epithelial ◽  
Infectious Diarrhea ◽  
Luminal Membrane ◽  
Inflammatory Bowel ◽  
Future Therapy

Abstract Background The transport of transepithelial Cl- and HCO3- is crucial for the function of the intestinal epithelium and maintains the acid-based homeostasis. Slc26a3 (DRA), as a key chloride-bicarbonate exchanger protein in the intestinal epithelial luminal membrane, participates in the electroneutral NaCl absorption of intestine, together with Na+/H+ exchangers. Increasing recent evidence supports the essential role of decreased DRA function or expression in infectious diarrhea and inflammatory bowel disease (IBD). Method In this review, we give an overview of the current knowledge of Slc26a3, including its cloning and expression, function, roles in infectious diarrhea and IBD, and mechanisms of actions. A better understanding of the physiological and pathophysiological relevance of Slc26a3 in infectious diarrhea and IBD may reveal novel targets for future therapy. Conclusion Understanding the physiological function, regulatory interactions, and the potential mechanisms of Slc26a3 in the pathophysiology of infectious diarrhea and IBD will define novel therapeutic approaches in future.

scholarly journals Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 126 ◽  
Author(s):  
Israr Khan ◽  
Naeem Ullah ◽  
Lajia Zha ◽  
Yanrui Bai ◽  
Ashiq Khan ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Gut Flora ◽  
Core Microbiome ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

scholarly journals A review of the pathogenesis of ankylosing spondylitis

2008 ◽  
Vol 24 (1) ◽  
pp. E2 ◽  
Author(s):  
Elias Dakwar ◽  
Jaypal Reddy ◽  
Fernando L. Vale ◽  
Juan S. Uribe
Keyword(s):  
Ankylosing Spondylitis ◽  
Strong Association ◽  
Critical Role ◽  
Axial Skeleton ◽  
Causative Role ◽  
Hla B27 ◽  
Pathogenic Role ◽  
The Past ◽  
New Findings

✓ Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited. Despite the strong association between human leukocyte antigen B27 (HLA-B27) and susceptibility to AS reported over the past 30 years, the exact pathogenic role of HLA-B27 in AS and other spondyloarthropathies has yet to be determined. The authors present a review of the literature pertaining to the pathogenesis of AS over the past several decades. Ankylosing spondylitis is a polygenic disorder, with HLA-B27 playing a critical causative role in its pathogenesis. Animal studies of the immunobiology of HLA-B27 have provided significant insight into the pathogenic role of HLA-B27. The search for the antigenic peptide to support the “arthritogenic peptide” hypothesis has been disappointing. Over the past decade there has been increasing interest in the critical role of the misfolding and unfolded protein response of the heavy chain HLA-B27 in the modulation of the inflammatory response. Although there have been significant new findings in the understanding of the pathogenesis of AS, the exact mechanisms have yet to be identified. There is considerable optimism that additional susceptibility genes, predisposing factors, and regulators of the inflammatory process will be identified that will provide avenues for future treatment.

scholarly journals POS1008 THE ROLE OF SERUM CALPROTECTIN IN THE DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE IN PATIENTS WITH ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 772-772
Author(s):  
P. Kulakova ◽  
G. Lukina ◽  
E. Alexandrova ◽  
A. Novikov ◽  
A. Klimets ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Longitudinal Study ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Аnkylosing spondylitis (AS) and inflammatory bowel diseases (IBD) have many common features. Approximately one in two patients with axial spondyloarthritis have subclinical (histologically confirmed) inflammation of the intestine, and 5-10% of subclinical inflammation turns into Crohn’s disease (CD) or Ulcerative colitis (UC) [1]. Colonoscopy is usually used to diagnose IBD, but this procedure is invasive. Laboratory biomarkers, as fecal calprotectin (FC) and serum calprotectin (SC) can used to diagnosis of IBD. But there is no consensus regarding SC clinical utility. SC is exposed to proteolytic enzymes, but its level also increases with inflammation in the intestine and is associated with a higher disease activity [2]. SC levels positively correlate with CRP, ESR, disease activity in AS, but not as obvious as with FC [3,4].Objectives:The aim of this study was to evaluate the possibility of using SC in the diagnosis of IBD in patients with AS.Methods:In the analysis were included 50 patients with AS, fulfilling the modified New York criteria, among them man -36 (72%), woman -14 (28%), mean age of patients was 42.5 ±9.9, mean disease duration – 13.4±8.7 years. All patients were examined with ESR, CRP, FC (range: 100-1800 µg /g), esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the SC level using ELISA (BUHLMANN MRP8/14 ELISA, range: 0.4-3.9 µg /ml).Results:All patients had a high disease activity, mean BASDAI was 5.3 ± 1.8, mean ASDAS CRP 3.7 ± 1.01, mean ASDAS ESR 3.6 ± 1.01. 80 % patients had high FC level (more than 100 µg / g), while only 18% patients had an increase of SC level. IBD were diagnosed in 11 cases: 6 patients (12 %) with CD and 5 patients (10 %) - UC, in the remaining cases (78%) was no intestinal pathology. Only 2 patients with IBD had a high SC level. SC level was more correlated with ESR (r=0.5) and CRP (r=0.5) (p <0.05) levels, than with FC level (r=0.4) (p <0.05).Conclusion:The results showed that there is currently insufficient data to assess the possibility of using SC in the diagnosis of IBD in patients with AS. There is a significant association between the SC, CRP and ESR, but not fecal calprotectin. Potentially SC may be more representative of systemic inflammation than an intestinal inflammation.References:[1]Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[2]Kalla R, Kennedy NA, Ventham NT, Boyapati RK, Adams AT, Nimmo ER, Visconti MR, Drummond H, Ho GT, Pattenden RJ, Wilson DC, Satsangi J. Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases. Am J Gastroenterol. 2016 Dec;111(12):1796-1805[3]Hu H, Du F, Zhang S, Zhang W. Serum calprotectin correlates with risk and disease severity of ankylosing spondylitis and its change during first month might predict favorable response to treatment. Mod Rheumatol. 2019 Sep;29(5):836-842.[4]Azramezani Kopi T, Shahrokh S, Mirzaei S, Asadzadeh Aghdaei H, Amini Kadijani A. The role of serum calprotectin as a novel biomarker in inflammatory bowel diseases: a review study. Gastroenterol Hepatol Bed Bench. 2019;12(3):183-189.Disclosure of Interests:None declared.

scholarly journals Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention

2021 ◽  
Vol 12 ◽  
Author(s):  
Marianna Lucafò ◽  
Debora Curci ◽  
Martina Franzin ◽  
Giuliana Decorti ◽  
Gabriele Stocco
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Process ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Pharmacological Prevention ◽  
Increased Risk ◽  
Inflammatory Bowel

Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.

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