| First Author | Silverman M | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 36 | Pages | 9671-9676 |
| PubMed ID | 28831005 | Mgi Jnum | J:250009 |
| Mgi Id | MGI:5921040 | Doi | 10.1073/pnas.1712280114 |
| Citation | Silverman M, et al. (2017) Protective major histocompatibility complex allele prevents type 1 diabetes by shaping the intestinal microbiota early in ontogeny. Proc Natl Acad Sci U S A 114(36):9671-9676 |
| abstractText | Certain MHC-II or HLA-D alleles dominantly protect from particular autoimmune diseases. For example, expression of the MHC-II Ealpha:Ebeta complex potently protects nonobese diabetic (NOD) mice, which normally lack this isotype, from spontaneous development of type 1 diabetes. However, the underlying mechanisms remain debated. We investigated MHC-II-mediated protection from type 1 diabetes using a previously reported NOD mouse line expressing an Ealpha transgene and, thereby, the Ealpha:Ebeta complex. Ealpha16/NOD females vertically protected their NOD offspring from diabetes and insulitis, an effect that was dependent on the intestinal microbiota; moreover, they developed autoimmunity when treated with certain antibiotics or raised in a germ-free environment. Genomic and proteomic analyses revealed NOD and Ealpha16/NOD mice to host mild but significant differences in the intestinal microbiotas during a critical early window of ontogeny, and transfer of cecal contents from the latter to the former suppressed insulitis. Thus, protection from autoimmunity afforded by particular MHC/HLA alleles can operate via intestinal microbes, highlighting potentially important societal implications of treating infants, or even just their pregnant mothers, with antibiotics. |
