CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes

Chikako Shimokawa (), Tamotsu Kato, Tadashi Takeuchi, Noriyasu Ohshima, Takao Furuki, Yoshiaki Ohtsu, Kazutomo Suzue, Takashi Imai, Seiji Obi, Alex Olia, Takashi Izumi, Minoru Sakurai, Hirokazu Arakawa, Hiroshi Ohno () and Hajime Hisaeda ()
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Chikako Shimokawa: National Institute of Infectious Disease
Tamotsu Kato: RIKEN Center for Integrative Medical Sciences
Tadashi Takeuchi: RIKEN Center for Integrative Medical Sciences
Noriyasu Ohshima: Gunma University
Takao Furuki: Center for Biological Resources and Informatics, Tokyo Institute of Technology
Yoshiaki Ohtsu: Gunma University
Kazutomo Suzue: Gunma University
Takashi Imai: Gunma University
Seiji Obi: Gunma University
Alex Olia: National Institute of Infectious Disease
Takashi Izumi: Gunma University
Minoru Sakurai: Center for Biological Resources and Informatics, Tokyo Institute of Technology
Hirokazu Arakawa: Gunma University
Hiroshi Ohno: RIKEN Center for Integrative Medical Sciences
Hajime Hisaeda: National Institute of Infectious Disease

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic β-cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8+ regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the intestinal microbiota and increases the abundance of Ruminococcus spp., resulting in the induction of CD8+ Treg cells. Furthermore, trehalose has therapeutic effects on both streptozotocin-induced diabetes and in the NOD mouse model of T1D. In addition, compared with healthy volunteers, patients with T1D have fewer CD8+ Treg cells, and the abundance of intestinal Ruminococcus positively correlates with the number of CD8+ Treg cells in humans.

Date: 2020
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DOI: 10.1038/s41467-020-15857-x

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