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Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice
Journal article   Open access   Peer reviewed

Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice

Eric V Marietta, Joseph A Murray, David H Luckey, Patricio R Jeraldo, Abhinav Lamba, Robin Patel, Harvinder S Luthra, Ashutosh Mangalam and Veena Taneja
Arthritis & rheumatology (Hoboken, N.J.), Vol.68(12), pp.2878-2888
12/2016
DOI: 10.1002/art.39785
PMCID: PMC5125894
PMID: 27337150
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https://www.ncbi.nlm.nih.gov/pmc/articles/5125894View
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Abstract

The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This study was undertaken to test the ability of a human gut-derived commensal to modulate immune response and treat arthritis in a humanized mouse model. We isolated a commensal bacterium, Prevotella histicola, that is native to the human gut and has systemic immune effects when administered enterally. Arthritis-susceptible HLA-DQ8 mice were immunized with type II collagen and treated with P histicola. Disease incidence, onset, and severity were monitored. Changes in gut epithelial proteins and immune response as well as systemic cellular and humoral immune responses were studied in treated mice. When treated with P histicola in prophylactic or therapeutic protocols, DQ8 mice exhibited significantly decreased incidence and severity of arthritis compared to controls. The microbial mucosal modulation of arthritis was dependent on regulation by CD103+ dendritic cells and myeloid suppressors (CD11b+Gr-1+ cells) and by generation of Treg cells (CD4+CD25+FoxP3+) in the gut, resulting in suppression of antigen-specific Th17 responses and increased transcription of interleukin-10. Treatment with P histicola led to reduced intestinal permeability by increasing expression of enzymes that produce antimicrobial peptides as well as tight junction proteins (zonula occludens 1 and occludin). However, the innate immune response via Toll-like receptor 4 (TLR-4) and TLR-9 was not affected in treated mice. Our results demonstrate that enteral exposure to P histicola suppresses arthritis via mucosal regulation. P histicola is a unique commensal that can be explored as a novel therapy for RA and may have few or no side effects.
 Flow Cytometry Arthritis, Experimental - genetics Intestinal Mucosa - metabolism Cell Proliferation Dendritic Cells - immunology Humans RNA, Messenger - metabolism HLA-DQ Antigens - immunology Intestines - immunology Occludin - metabolism T-Lymphocytes, Regulatory - immunology Toll-Like Receptor 9 - immunology Prevotella - immunology Intestinal Mucosa - immunology Zonula Occludens-1 Protein - metabolism Cytokines - genetics Chemokines - immunology Cytokines - immunology Mice, Transgenic Arthritis, Experimental - immunology Toll-Like Receptor 4 - immunology Intestinal Mucosa - microbiology Permeability Reverse Transcriptase Polymerase Chain Reaction Chemokines - genetics Arthritis, Rheumatoid - genetics Animals Intestines - microbiology HLA-DQ Antigens - genetics Interleukin-10 - genetics Th17 Cells - immunology Mice Gastrointestinal Microbiome - immunology Arthritis, Rheumatoid - immunology Interleukin-10 - immunology Prevotella melaninogenica - immunology

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