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Interactions between AHR ligands and the gut microbiota in murine arthritis

AHR 配体与小鼠关节炎肠道微生物群之间的相互作用

基本信息

批准号：
8765363
负责人：
Matthew L Stoll
金额：
$ 18.38万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8765363
关键词：
Affect Age Alabama Aldehydes Amino Acids Animal Model Ankle Antibodies Aromatic Hydrocarbons Arthritis Aryl Hydrocarbon Receptor Attenuated Autoimmune Diabetes Autoimmune Diseases Autoimmune Process Autoimmunity Bacteria Binding Cell physiology Cells Child Childhood Crohn&apos s disease Cross-Sectional Studies Data Dependence Development Dioxins Disease Enteral Environmental Risk Factor Etiology Exposure to Family Genes Genetic Germ-Free Glucosephosphate Isomerase Gnotobiotic Human Indole-3-Carbinol Indoles Inflammatory Inflammatory Bowel Diseases Interleukin-17 Interleukins Intestines Lactobacillus Lead Ligand Binding Light Link Maintenance Malignant Neoplasms Modeling Mus Neonatal Pathogenesis Patients Pattern Perinatal Phenotype Play Polychlorinated Biphenyls Population Principal Investigator Production Regulatory T-Lymphocyte Research Personnel Rheumatoid Arthritis Risk Risk Factors Role Severities Spondylarthritis Spondylitis Study Subject T-Lymphocyte Testing Tetrachlorodibenzodioxin Thick Transplantation Tryptophan United States Universities Up-Regulation Work aryl hydrocarbon receptor ligand bisphenol A cigarette smoking disease phenotype enteric feeding gut microbiota human subject improved mouse model programs public health relevance transcription factor

项目摘要

DESCRIPTION (provided by applicant): Spondyloarthritis (SpA) affects 0.5-2% of the population in the United States and is characterized by an asymmetric inflammatory arthritis, spondylitis, and enthesitis, with risk of extra-articular complications. The pathogenesis is unknown; however, despite recent genetic advances, there remains an important role for environmental triggers. One potential contributing factor is the intestinal microbiota, abnormalities in which are linked to inflammatory bowel disease. Another important environmental factor that is wrongly linked to animal models of arthritis but has not yet been studied in spondyloarthritis is the family of aryl hydrocarbon receptor ligands. It is our hypothess that both the enteric microbiota and AHR ligands contribute towards spondyloarthritis, and furthermore that the microbiota can attenuate the effects of the AHR ligands. The studies proposed herein will shed important light on these potential triggers. First, the investigators wil feed enteric microbiota from human subjects to a mouse model of arthritis, to determine whether the microbiota from arthritis patients is more effective at inducing arthritis. Second, the investigators will expose the same mice prenatally with multiple different AHR ligands to evaluate the effect of AHR ligand exposure on development of arthritis. The AHR studies will be repeated in the germ-free state, to evaluate whether the microbiota can modulate the effect of AHR ligand exposure.

描述（由申请人提供）：在美国，脊椎关节炎（SpA）影响了0.5-2%的人口，其特征是不对称炎症性关节炎、脊柱炎和脊椎炎，有关节外并发症的风险。发病机制尚不清楚；然而，尽管最近遗传方面取得了进展，但环境因素仍然发挥着重要作用。一个潜在的影响因素是肠道微生物群，其异常与炎症性肠病有关。另一个被错误地与关节炎动物模型联系在一起但尚未在脊椎关节炎中研究的重要环境因素是芳烃受体配体家族。我们的假设是，肠道微生物群和AHR配体都有助于脊柱关节炎，而且微生物群可以减弱AHR配体的作用。本文提出的研究将对这些潜在的触发因素提供重要的启示。首先，研究人员将把来自人类受试者的肠道微生物群喂给关节炎小鼠模型，以确定来自关节炎患者的微生物群是否更有效地诱导关节炎。其次，研究人员将在相同的小鼠产前暴露于多种不同的AHR配体，以评估AHR配体暴露对关节炎发展的影响。AHR研究将在无菌状态下重复进行，以评估微生物群是否可以调节AHR配体暴露的影响。