scholarly journals Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Vuerich ◽  
Na Wang ◽  
Ahmadreza Kalbasi ◽  
Jonathon J. Graham ◽  
Maria Serena Longhi
Keyword(s):  
Autoimmune Hepatitis ◽  
Immune Regulation ◽  
Th17 Cells ◽  
Inflammatory Responses ◽  
Calcineurin Inhibitors ◽  
Inflammatory Disorder ◽  
Disease Relapse ◽  
Regulatory Cells ◽  
Chronic Inflammatory Disorder ◽  
Therapeutic Tools

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological features of interface hepatitis. AIH therapeutic management still relies on the administration of corticosteroids, azathioprine and other immunosuppressants like calcineurin inhibitors and mycophenolate mofetil. Withdrawal of immunosuppression often results in disease relapse, and, in some cases, therapy is ineffective or associated with serious side effects. Understanding the mechanisms underlying AIH pathogenesis is therefore of paramount importance to develop more effective and well tolerated agents capable of restoring immunotolerance to liver autoantigens. Imbalance between effector and regulatory cells permits liver damage perpetuation and progression in AIH. Impaired expression and regulation of CD39, an ectoenzyme key to immunotolerance maintenance, have been reported in Tregs and effector Th17-cells derived from AIH patients. Interference with these altered immunoregulatory pathways may open new therapeutic avenues that, in addition to limiting aberrant inflammatory responses, would also reconstitute immune homeostasis. In this review, we highlight the most recent findings in AIH immunopathogenesis and discuss how these could inform and direct the development of novel therapeutic tools.

scholarly journals Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yingli Zhang ◽  
Rongrong Liang ◽  
Aicen Xie ◽  
Wenqian Shi ◽  
Huarong Huang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Inflammatory Disorder ◽  
Mrna Levels ◽  
T Helper 17 ◽  
Mucus Production ◽  
Chronic Inflammatory Disorder ◽  
Extracellular Loops

Asthma is a heterogeneous chronic inflammatory disorder of the airways with a complex etiology, which involves a variety of cells and cellular components. Therefore, the aim of the study was to investigate the effects and mechanisms of antagonistic peptides that specifically bind to the first and second extracellular loops of CCR5 (GH and HY peptides, respectively) and anti-interleukin-23 subunit p19 (anti-IL-23p19) in the airway and thereby mediate inflammation and the IL-23/T helper 17 (Th17) cell pathway in asthmatic mice. An experimental asthma model using BALB/c mice was induced by ovalbumin (OVA) and treated with peptides that are antagonistic to CCR5 or with anti-IL-23p19. The extents of the asthmatic inflammation and mucus production were assessed. In addition, bronchoalveolar lavage fluid (BALF) was collected, the cells were counted, and the IL-4 level was detected by ELISA. The IL-23/Th17 pathway-related protein and mRNA levels in the lung tissues were measured, and the positive production rates of Th17 cells in the thymus, spleen, and peripheral blood were detected. The groups treated with one of the two peptides and/or anti-IL-23p19 showed significant reductions in allergic inflammation and mucus secretion; decreased expression levels of IL-23p19, IL-23R, IL-17A and lactoferrin (LTF); and reduced proportions of Th17 cells in the thymus, spleen, and peripheral blood. Specifically, among the four treatment groups, the anti-IL-23p19 with HY peptide group exhibited the lowest positive production rate of Th17 cells. Our data also showed a significant and positive correlation between CCR5 and IL-23p19 protein expression. These findings suggest that the administration of peptides antagonistic to CCR5 and/or anti-IL-23p19 can reduce airway inflammation in asthmatic mice, most likely through inhibition of the IL-23/Th17 signaling pathway, and the HY peptide can alleviate inflammation not only through the IL-23/Th17 pathway but also through other mechanisms that result in the regulation of inflammation.

scholarly journals Interleukin-23 drives innate and T cell–mediated intestinal inflammation

2006 ◽  
Vol 203 (11) ◽  
pp. 2473-2483 ◽  
Author(s):  
Sophie Hue ◽  
Philip Ahern ◽  
Sofia Buonocore ◽  
Marika C. Kullberg ◽  
Daniel J. Cua ◽  
...  
Keyword(s):  
T Cell ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Adaptive Immune ◽  
Proinflammatory Responses ◽  
Interleukin 23 ◽  
Immune Pathology ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract involving aberrant activation of innate and adaptive immune responses. We have used two complementary models of IBD to examine the roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal inflammation. Our results clearly show that IL-23, but not IL-12, is essential for the induction of chronic intestinal inflammation mediated by innate or adaptive immune mechanisms. Depletion of IL-23 was associated with decreased proinflammatory responses in the intestine but had little impact on systemic T cell inflammatory responses. These results newly identify IL-23 as a driver of innate immune pathology in the intestine and suggest that selective targeting of IL-23 represents an attractive therapeutic approach in human IBD.

scholarly journals Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuting Wen ◽  
Long He ◽  
Zhuotai Zhong ◽  
Runyuan Zhao ◽  
Senhui Weng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Th17 Cells ◽  
Experimental Colitis ◽  
Short Chain Fatty Acids ◽  
Peroxisome Proliferator ◽  
Inflammatory Disorder ◽  
T Helper 17 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Chronic Inflammatory Disorder ◽  
Immune Imbalance

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naïve CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPARγ) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPARγ activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.

Functional foods and nutraceuticals as therapeutic tools for the treatment of diet-related diseases

2013 ◽  
Vol 91 (6) ◽  
pp. 387-396 ◽  
Author(s):  
Thea Magrone ◽  
Fatima Perez de Heredia ◽  
Emilio Jirillo ◽  
Giuseppa Morabito ◽  
Ascension Marcos ◽  
...  
Keyword(s):  
Functional Foods ◽  
T Regulatory Cells ◽  
Inflammatory Responses ◽  
Sedentary Lifestyle ◽  
Clinical Applications ◽  
Low Grade ◽  
Regulatory Cells ◽  
Related Disease ◽  
Therapeutic Tools ◽  
Low Grade Inflammation

In Western societies, the incidence of diet-related diseases is progressively increasing due to greater availability of hypercaloric food and a sedentary lifestyle. Obesity, diabetes, atherosclerosis, and neurodegeneration are major diet-related pathologies that share a common pathogenic denominator of low-grade inflammation. Functional foods and nutraceuticals may represent a novel therapeutic approach to prevent or attenuate diet-related disease in view of their ability to exert anti-inflammatory responses. In particular, activation of intestinal T regulatory cells and homeostatic regulation of the gut microbiota have the potential to reduce low-grade inflammation in diet-related diseases. In this review, clinical applications of polyphenol-rich functional foods and nutraceuticals in postprandial inflammation, obesity, and ageing will be discussed. We have placed special emphasis on polyphenols since they are broadly distributed in plants.

Concurrent autoimmune hepatitis in multiple sclerosis

2017 ◽  
Vol 24 (3) ◽  
pp. 350-353 ◽  
Author(s):  
Gonçalo Cação ◽  
Ernestina Santos ◽  
Ana Martins Silva
Keyword(s):  
Multiple Sclerosis ◽  
Liver Biopsy ◽  
Autoimmune Hepatitis ◽  
Interferon Beta ◽  
Immunosuppressive Treatment ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Rare Association ◽  
Disease Modifying Therapy ◽  
Disease Modifying

Background: Autoimmune hepatitis (AIH) is a rare and chronic inflammatory disorder associated with extrahepatic autoimmune diseases, including, infrequently, multiple sclerosis (MS). Short Reports: We report five cases of MS and AIH association. One patient developed AIH while under interferon beta-1b and the remaining while off disease-modifying therapy, although after methylprednisolone bolus in three. All presented a liver biopsy compatible with AIH. Hepatitis resolution was achieved with immunosuppressive treatment, but one patient died after a fulminant hepatitis requiring liver transplant. Discussion: A thorough review of published cases supports this clear, although rare, association and a liver biopsy should be considered in AIH suspected cases.

scholarly journals Interleukin 17 receptor E identifies heterogeneous T helper 17 cells in peritoneal fluid of severe endometriosis patients

2021 ◽  
Author(s):  
Yanping Jiang ◽  
Lu Wang ◽  
Yaqin Peng ◽  
Jian Qin ◽  
Aili Tan ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Th17 Cells ◽  
Molecular Mechanisms ◽  
Interleukin 17 ◽  
Inflammatory Disorder ◽  
T Helper ◽  
T Helper 17 ◽  
Chronic Inflammatory Disorder ◽  
Gm Csf ◽  
Metabolic Heterogeneity

Endometriosis is a chronic inflammatory disorder resulting in pelvic pain and infertility. The role of T helper 17 (Th17) cells in endometriosis remains elusive. In this study, through detecting CXCR3, CCR4, CCR10, CCR6, interleukin-17 Receptor E (IL-17RE), and CD27, live RORγt-and-IL-17A-expressing Th17 cells were distinguished and sorted from peritoneal fluid (PF) of patients with stage III and IV endometriosis. Furthermore, we found that IL-17RE and CD27 were the labels of heterogeneous PF Th17 subsets, i.e. IL-17RE-CD27- subset, IL-17RE+CD27- subset, and IL-17RE+CD27+ subset. The former two subsets expressed higher IL-17A, GM-CSF, and IL-22 and were more proliferative than the latter subset. RNA-Seq analysis on IL-17RE+ Th17 subset and IL-17RE- Th17 subset revealed up-regulation of genes involved in oxidative phosphorylation and electron transport chain in IL-17RE+ Th17 subset relative to IL-17RE- Th17 subset. Consistently, the IL-17RE+ Th17 subset produced more adenosine triphosphate (ATP) and reactive oxygen species (ROS) than IL-17RE- Th17 subset. In conclusion, this study provides a novel method to detect and isolate live PF Th17 cells from endometriosis patients and unveils the functional and metabolic heterogeneity of PF Th17 subsets. Therefore, it sheds light on the elucidation of molecular mechanisms that modulate the function of pathological Th17 cells in endometriosis.

scholarly journals Autoimmune Hepatitis: Shifts in Gut Microbiota and Metabolic Pathways among Egyptian Patients

2020 ◽  
Vol 8 (7) ◽  
pp. 1011
Author(s):  
Nahla M. Elsherbiny ◽  
Mohammed Rammadan ◽  
Elham A. Hassan ◽  
Mohamed E. Ali ◽  
Abeer S. Abd El-Rehim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Autoimmune Hepatitis ◽  
Metabolic Pathways ◽  
Large Scale ◽  
Rrna Gene ◽  
Inflammatory Disorder ◽  
Healthy Individuals ◽  
Variable Regions ◽  
Chronic Inflammatory Disorder ◽  
Egyptian Patients

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder with complex immunopathogenesis. Dysbiosis has been linked to many autoimmune diseases, but its detailed role in autoimmune hepatitis (AIH) still needs rigorous evaluation, especially in Egypt. We aimed to identify the shift in the gut microbiota profile and resultant metabolic pathways in AIH Egyptian patients compared to healthy individuals. Stool samples were collected from 15 AIH-naive patients and from 10 healthy individuals. The V3-V4 hyper-variable regions in16S rRNA gene was amplified and sequenced using Illumina MiSeq platform. Significantly lower bacterial diversity in AIH patients was found compared to the controls. A phylum-level analysis showed the overrepresentation of Firmicutes, Bacteroides, and Proteobacteria. At the genus level, AIH-associated enrichment of Faecalibacterium, Blautia, Streptococcus, Haemophilus, Bacteroides, Veillonella, Eubacterium, Lachnospiraceae and Butyricicoccus was reported in contrast to Prevotella, Parabacteroides and Dilaster, which were significantly retracted in such patients. Overall, the predicted metabolic pathways associated with dysbiosis in AIH patients could orchestrate the potential pathogenic roles of gut microbiota in autoimmune disease, though not in a disease-specific manner, calling for future large-scale studies.

scholarly journals Autoimmune Hepatitis: A Review of Current Diagnosis and Treatment

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Ashima Makol ◽  
Kymberly D. Watt ◽  
Vaidehi R. Chowdhary
Keyword(s):  
Autoimmune Hepatitis ◽  
Immunosuppressive Agents ◽  
Clinical Manifestations ◽  
Normal Liver ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Initiation Of Therapy ◽  
Long Term Prognosis ◽  
Indolent Disease

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease. Corticosteroid therapy must be instituted early and modified in an individualized fashion. Treatment decisions are often complicated by the diverse clinical manifestations, uncertainty about natural history, evolving ideas about treatment end points, and a multitude of alternative immunosuppressive agents. Achieving normal liver tests and tissue is the ideal treatment end point, but needs to be weighed against the risk of side effects. Decompensated patients may benefit from early liver transplantation. Long-term prognosis is excellent with early and aggressive initiation of therapy. Our paper discusses AIH, giving a detailed overview of its clinical presentation, risk factors, immunopathogenesis, up-to-date diagnostic criteria, current updates in therapy with a brief discussion of AIH in pregnancy, and long-term implications for cirrhosis and hepatocellular carcinoma in AIH patients.

Secukinumab and Apremilast Combination Therapy for Recalcitrant Psoriasis

2017 ◽  
Vol 2 (2) ◽  
pp. 59-61 ◽  
Author(s):  
Ali Hadi ◽  
Mark Lebwohl
Keyword(s):  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Psoriatic Arthritis ◽  
Th17 Cells ◽  
Treatment Options ◽  
Inflammatory Disorder ◽  
Combination Therapies ◽  
Chronic Inflammatory Disorder ◽  
Increased Risk ◽  
Artery Disease

Psoriasis is a chronic inflammatory disorder of the skin and joints mediated by aberrant activity of Th1 and Th17 cells. It also has been shown to be associated with an increased risk of coronary artery disease and metabolic syndrome, highlighting the associated systemic inflammation. Despite the multitude of treatment options available, some cases are still refractory to the available agents, necessitating innovative combination therapies for management. Here we report the second case of plaque psoriasis and psoriatic arthritis treated successfully with a combination of apremilast and secukinumab.

scholarly journals Autoimmune Hepatitis: A Review with emphasis on its histomorphology

2012 ◽  
Vol 2 (4) ◽  
pp. 317-323
Author(s):  
SV Pradhan
Keyword(s):  
Autoimmune Hepatitis ◽  
Hepatitis A ◽  
Clinical Presentation ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Immune Mediated ◽  
Toxic Drug ◽  
Clinical Presentations ◽  
Histomorphological Changes ◽  
Indolent Disease

Autoimmune hepatitis is a chronic inflammatory disorder characterized by periportal inflammation, hypergammaglobulinemia with elevated autoantibodies, and a dramatic response to immunosuppression. Various environmental and genetic influences can trigger the immune mediated destruction of the liver. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure. Autoimmune hepatitis does not have a pathognomonic feature, and its laboratory, serologic, and histologic manifestations are found in acute and chronic liver disease of diverse causes. Difficulties in distinguishing toxic, drug-related, virus-induced, and autoimmune causes of severe acute liver injury can result in misclassification. Our paper discusses autoimmune hepatitis, giving a detailed overview of its clinical presentation, immunopathogenesis, emphasis on histomorphological changes and the diagnostic criteria.Journal of Pathology of Nepal (2012) Vol. 2, 317-323DOI: http://dx.doi.org/10.3126/jpn.v2i4.6887

Sign in / Sign up

Export Citation Format

Share Document