ERAP1 deficient mice have reduced Type 1 regulatory T cells and develop skeletal and intestinal features of Ankylosing Spondylitis.

Autor: Pepelyayeva Y; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Rastall DPW; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Aldhamen YA; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., O'Connell P; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Raehtz S; Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA., Alyaqoub FS; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Blake MK; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Raedy AM; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Angarita AM; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Abbas AM; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Pereira-Hicks CN; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., Roosa SG; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA., McCabe L; Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.; Department of Radiology, Michigan State University, East Lansing, MI, 48824, USA.; Biomedical Imaging Research Center, Michigan State University, East Lansing, MI, 48824, USA., Amalfitano A; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA. amalfit1@msu.edu.; Department of Pediatrics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, 48824, USA. amalfit1@msu.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Aug 20; Vol. 8 (1), pp. 12464. Date of Electronic Publication: 2018 Aug 20.
DOI: 10.1038/s41598-018-30159-5
Abstrakt: Ankylosing spondylitis (AS) is a prototypical sero-negative autoimmune disease that affects millions worldwide. Single nucleotide polymorphisms in the Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) gene have been linked to AS via GWAS studies, however, the exact mechanism as to how ERAP1 contributes to pathogenesis of AS is not understood. We undertook µCT imaging and histologic analysis to evaluate bone morphology of the axial skeletons of ERAP1 -/- mice and discovered the hallmark skeletal features of AS in these mice, including spinal ankylosis, osteoporosis, and spinal inflammation. We also confirmed the presence of spontaneous intestinal dysbiosis and increased susceptibility to Dextran Sodium Sulfate (DSS)-induced colitis in ERAP1 -/- mice, however the transfer of healthy microbiota from wild type mice via cross-fostering experiments did not resolve the skeletal phenotypes of ERAP1 -/- mice. Immunological analysis demonstrated that while ERAP1 -/- mice had normal numbers of peripheral Foxp3 + Tregs, they had reduced numbers of both "Tr1-like" regulatory T cells and tolerogenic dendritic cells, which are important for Tr1 cell differentiation. Together, our data suggests that ERAP1 -/- mice may serve as a useful animal model for studying pathogenesis of intestinal, skeletal, and immunological manifestations of Ankylosing Spondylitis.
Databáze: MEDLINE
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