PNAS [IF:11.205]

Protective major histocompatibility complex allele prevents type 1 diabetes by shaping the intestinal microbiota early in ontogeny

保护性主要组织相容性复合物等位基因通过塑形早期个体发生学肠道菌群而预防1型糖尿病

10.1073/pnas.1712280114

2017-08-22, Article

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Certain MHC-II or HLA-D alleles dominantly protect from particular autoimmune diseases. For example, expression of the MHC-II Eα:Eβ 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 Eα transgene and, thereby, the Eα:Eβ complex. Eα16/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 Eα16/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.

First Authors:
Michael Silverman

Correspondence Authors:
Diane Mathis

All Authors:
Michael Silverman,Lindsay Kua,Alessandro Tanca,Mauro Pala,Antonio Palomba,Ceylan Tanes,Kyle Bittinger,Sergio Uzzau,Christophe Benoist,Diane Mathis