Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity

Cell Host & Microbe, Journal Year: 2019, Volume and Issue: 26(1), P. 100 - 113.e8

Published: June 18, 2019

Language: Английский

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Impaired B‐cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies

Immunological Reviews, Journal Year: 2019, Volume and Issue: 292(1), P. 90 - 101

Published: Nov. 1, 2019

Abstract A role for B cells in autoimmune diseases is now clearly established both mouse models and humans by successful treatment of multiple sclerosis rheumatoid arthritis with anti‐CD20 monoclonal antibodies that eliminate cells. However, the underlying mechanisms which promote development remain poorly understood. Here, we review evidence patients disease suffer from defects early B‐cell tolerance checkpoints therefore fail to counterselect developing autoreactive These are primary may result altered receptor signaling dysregulated T‐cell/regulatory T‐cell compartment. As a consequence, large numbers naive accumulate blood autoimmunity through presentation self‐antigen T In addition, new suggests this reservoir contains clones develop into CD27 − CD21 −/lo associated increased severity plasma secreting potentially pathogenic autoantibodies after acquisition somatic hypermutations improve affinity self‐antigens.

Language: Английский

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Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus

Molecular Medicine, Journal Year: 2019, Volume and Issue: 25(1)

Published: Aug. 1, 2019

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic environmental factors. The purpose of this study to identify the influence gut microbiota in pathogenesis SLE, investigate mechanism involved.Fecal from C57/BL6 mice SLE prone were examined using next-generation sequencing (NGS). Germ free given fecal transplantation (FMT), their microbiome gene expression recipients' colons NGS. anti-double stranded DNA (anti-dsDNA) antibodies recipients determined an enzyme-linked immunosorbent assay (ELISA). immune cell profiles analyzed flow cytometry at 3rd week after FMT, genes associated with FMT was quantitative real-time PCR (qRT-PCR).The had lower community richness diversity than healthy mice. Fecal recipient similar donors. could lead significant increase anti-dsDNA promote response Our results also indicated that resulted changes distribution cells upregulated certain susceptibility genes.SLE alterations microbiota. can induce production germ stimulate inflammatory response, alter these

Language: Английский

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Gut Microbiome and Metabolites in Systemic Lupus Erythematosus: Link, Mechanisms and Intervention

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 15, 2021

Systemic lupus erythematosus (SLE), often considered the prototype of autoimmune diseases, is characterized by over-activation system with abnormal functions innate and adaptive immune cells production a large number autoantibodies against nuclear components. Given highly complex heterogeneous nature SLE, pathogenesis this disease remains incompletely understood presumed to involve both genetic environmental factors. Currently, disturbance gut microbiota has emerged as novel player involved in SLE. With in-depth research, understanding intestinal bacteria-host interaction SLE much more comprehensive. Recent years have also seen an increase metabolomics studies attempt identify potential biomarkers for diagnosis or activity monitoring. An intricate relationship between microbiome changes metabolic alterations could help explain mechanisms which bacteria play roles Here, we review role dysbiosis aetiology how interact host metabolism axis. A proposed treatment strategy based on (GM) regulation discussed review. Increasing our their function will provide us opportunities develop effective precise diagnostic strategies explore microbiota-based treatments patients lupus.

Language: Английский

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Recent Advances in Our Understanding of the Link between the Intestinal Microbiota and Systemic Lupus Erythematosus

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(19), P. 4871 - 4871

Published: Sept. 30, 2019

Systemic lupus erythematosus (SLE) is an autoimmune disease featuring enhanced expression of type I interferon (IFN) and autoantibody production triggering inflammation of, damage to, multiple organs. Continuing research efforts focus on how gut microbes trigger systemic autoimmunity SLE. The microbial communities mice humans with have been investigated via high-throughput sequencing. Firmicutes-to-Bacteroidetes ratio consistently reduced in SLE patients, regardless ethnicity. relative abundance Lactobacillus differs from the animal model used (MRL/lpr or NZB/W F1 mice). This may indicate that interactions between host, rather than enrichment certain microbes, are especially significant terms development. Enterococcus gallinarum reuteri, both which possible pathobionts, become translocated into tissue if epithelial barrier impaired. then interact host immune systems, activating IFN pathway inducing production. In addition, molecular mimicry critically link microbiome to Gut commensals patients share protein epitopes Ro60 autoantigen. Ruminococcus gnavus strain cross-reacted native DNA, anti-double-stranded DNA antibody response. Expansion R. paralleled increase activity nephritis. Such insights microbiota enhance our understanding pathogenesis will identify biomarkers predicting active disease.

Language: Английский

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