ERAP1 deficient mice have reduced Type 1 regulatory T cells and develop skeletal and intestinal features of Ankylosing Spondylitis
| Autor: | Patrick O'Connell, Maja K. Blake, Yasser A. Aldhamen, Ariana M Angarita, Fadel S. Alyaqoub, David P W Rastall, Yuliya Pepelyayeva, Sarah G Roosa, Cristiane Pereira-Hicks, Sandra Raehtz, Laura R. McCabe, Abdulraouf M Abbas, Ashley M Raedy, Andrea Amalfitano |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine lcsh:Medicine Inflammation Biology Aminopeptidases Polymorphism Single Nucleotide T-Lymphocytes Regulatory Article Minor Histocompatibility Antigens Pathogenesis Mice 03 medical and health sciences medicine Animals Genetic Predisposition to Disease Spondylitis Ankylosing Colitis lcsh:Science Spondylitis Mice Knockout Autoimmune disease Ankylosing spondylitis Multidisciplinary lcsh:R FOXP3 Forkhead Transcription Factors medicine.disease 3. Good health Mice Inbred C57BL Phenotype 030104 developmental biology Immunology Dysbiosis lcsh:Q medicine.symptom |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30159-5 |
| Popis: | 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: | OpenAIRE |
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