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Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota

Li, Y. Y., Pearson, J. A., Chao, C., Peng, J., Zhang, X., Zhou, Z., Liu, Y., Wong, Florence Susan and Wen, L. 2017. Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) modulates T1DM susceptibility by gut microbiota. Journal of Autoimmunity 82 , pp. 85-95. 10.1016/j.jaut.2017.05.007

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Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) is an innate immune receptor. To investigate the role of Nod2 in susceptibility to the autoimmune disease, type 1 diabetes mellitus (T1DM), we generated Nod2-/- non-obese diabetic (NOD) mice. The Nod2-/-NOD mice had different composition of the gut microbiota compared to Nod2+/+NOD mice and were significantly protected from diabetes, but only when housed separately from Nod2+/+NOD mice. This suggested that T1DM susceptibility in Nod2-/-NOD mice is dependent on the alteration of gut microbiota, which modulated the frequency and function of IgA-secreting B-cells and IL-10 promoting T-regulatory cells. Finally, colonizing germ-free NOD mice with Nod2-/-NOD gut microbiota significantly reduced pro-inflammatory cytokine-secreting immune cells but increased T-regulatory cells. Thus, gut microbiota modulate the immune system and T1D susceptibility. Importantly, our study raises a critical question about the housing mode in the interpretation of the disease phenotype of genetically-modified mouse strains in T1DM studies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0896-8411
Date of First Compliant Deposit: 10 July 2017
Date of Acceptance: 25 May 2017
Last Modified: 14 May 2020 11:00

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