创作:花开 审核:aluba 2017年09月10日
  • 利用表达MHCII Eα:Eβ复合物的非肥胖糖尿病(NOD)小鼠作为研究模型;
  • Eα16可对NOD雌鼠的后代在糖尿病和胰岛炎中起保护作用,该作用依赖于肠道菌群,抗生素处理或置于无菌环境喂养则产生自身免疫性疾病;
  • 基因组学及蛋白质组学分析揭示,个体发生早期阶段的NOD和Eα16/NOD小鼠肠道菌群不同,将Eα16/NOD小鼠盲肠内容转移至NOD小鼠,抑制胰岛炎的发生;
  • MHC/HLA等位基因通过肠道菌群保护个体避免发生自身免疫性疾病。
PNAS [IF:11.205]

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



2017-08-22, Article

Abstract & Authors:展开

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