938-P: A Human Gut Commensal, Parabacteroides Distasonis, Enhances Type 1 Diabetes Autoimmunity via Molecular Mimicry
| العنوان: | 938-P: A Human Gut Commensal, Parabacteroides Distasonis, Enhances Type 1 Diabetes Autoimmunity via Molecular Mimicry |
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| المؤلفون: | William Kwok, C. Ronald Kahn, Emrah Altindis, Claudia Brady, I-Ting Chow, Qian Huang, Amol Raisingani, Khyati Girdhar, Tu Tran, Mark A. Atkinson |
| المصدر: | Diabetes. 70 |
| بيانات النشر: | American Diabetes Association, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Autoimmune disease, Adoptive cell transfer, biology, Endocrinology, Diabetes and Metabolism, Nod, Gut flora, medicine.disease_cause, biology.organism_classification, medicine.disease, Autoimmunity, Molecular mimicry, Immunology, Internal Medicine, medicine, Parabacteroides distasonis, NOD mice |
| الوصف: | Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of pancreatic β-cells by autoreactive T-cells. Genome-wide association studies (GWAS) have identified over 150 regions that influence the risk of developing T1D, but genetics alone cannot account for the increasing incidence of T1D. Various environmental factors have been examined to identify their potential contributions, however, no report has demonstrated a direct role of these environmental factors in T1D onset. In the nonobese diabetic (NOD) mouse model of T1D, over 90% of the anti-insulin CD4+ T-cell clones target amino acids 9-23 of the insulin B chain (insB:9-23). More importantly, insB:9-23 specific T-cells have been identified in islets obtained from human organ donors with T1D as well as peripheral blood lymphocytes of living T1D patients. In this study, focusing on the main insulin epitope, insB:9-23, we explored whether a microbial insB:9-23 mimic could modulate T1D. We demonstrate that a microbial insB:9-23 mimic of Parabacteroides distasonis, a human gut commensal, exclusively stimulates NOD mouse T-cells specific to insB:9-23. Indeed, immunization of NOD mice with either the bacterial mimic peptide or insB:9-23 further verified the cross-reactivity in vivo. P. distasonis colonization of the female NOD mice gut accelerated T1D onset. In addition, adoptive transfer of splenocytes from NOD mice colonized with P. distasonis to NOD.SCID recipients conferred the enhanced disease phenotype. Integration analysis of published DIABIMMUNE T1D gut microbiome data revealed that P. distasonis is lacking in the gut microbiota of the children below age 1 who will eventually develop T1D in Russia and Estonia. Notably, P. distasonis insB:9-23 mimic can stimulate human T-cell clones specific to insB:9-23. Taken together, our studies define a potential molecular mimicry link between T1D pathogenesis and the gut microbiota. Disclosure K. Girdhar: None. E. Altindis: None. Q. Huang: None. I. Chow: None. C. Brady: None. A. Raisingani: None. T. Tran: None. W. Kwok: None. M. A. Atkinson: None. C. Kahn: Advisory Panel; Self; ERX Pharmaceuticals, Kaleido Biosciences, Inc., Consultant; Self; Flagship Pioneering, Sana/Cobalt. Funding National Institutes of Health (1K01DK117967-01, R01DK031026, R01DK033201, P01AI042288); G. Harold & Leila Y. Mathers Foundation; Iacocca Family Foundation |
| تدمد: | 1939-327X 0012-1797 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::b3e704fc0f3fecc12ce0e5eed536d865 https://doi.org/10.2337/db21-938-p |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........b3e704fc0f3fecc12ce0e5eed536d865 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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