Asset Details
Do you wish to reserve the book?
A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes
Do you wish to request the book?
A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
A gut microbial peptide and molecular mimicry in the pathogenesis of type 1 diabetes
2022
Overview
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of autoantibodies and T cells directed at an epitope in the B-chain of insulin (insB:9–23). Analysis of microbial protein sequences with homology to the insB:9–23 sequence revealed 17 peptides showing >50% identity to insB:9–23. Of these 17 peptides, the hprt4–18 peptide, found in the normal human gut commensal Parabacteroides distasonis, activated both human T cell clones from T1D patients and T cell hybridomas from nonobese diabetic (NOD) mice specific to insB:9–23. Immunization of NOD mice with P. distasonis insB:9–23 peptide mimic or insB:9–23 peptide verified immune cross-reactivity. Colonization of female NOD mice with P. distasonis accelerated the development of T1D, increasing macrophages, dendritic cells, and destructive CD8+ T cells, while decreasing FoxP3+ regulatory T cells. Western blot analysis identified P. distasonis–reacting antibodies in sera of NOD mice colonized with P. distasonis and human T1D patients. Furthermore, adoptive transfer of splenocytes from P. distasonis–treated mice to NOD/SCID mice enhanced disease phenotype in the recipients. Finally, analysis of human children gut microbiome data from a longitudinal DIABIMMUNE study revealed that seroconversion rates (i.e., the proportion of individuals developing two or more autoantibodies) were consistently higher in children whose microbiome harbored sequences capable of producing the hprt4–18 peptide compared to individuals who did not harbor it. Taken together, these data demonstrate the potential role of a gut microbiota-derived insB:9–23-mimic peptide as a molecular trigger of T1D pathogenesis.
