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

ABSTRACT: Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic ?-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.

SUBMITTER: Shimokawa C

PROVIDER: S-EPMC7176710 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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CD8<sup>+</sup> regulatory T cells are critical in prevention of autoimmune-mediated diabetes.

Shimokawa Chikako C Kato Tamotsu T Takeuchi Tadashi T Ohshima Noriyasu N Furuki Takao T Ohtsu Yoshiaki Y Suzue Kazutomo K Imai Takashi T Obi Seiji S Olia Alex A Izumi Takashi T Sakurai Minoru M Arakawa Hirokazu H Ohno Hiroshi H Hisaeda Hajime H

Nature communications 20200422 1

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<sup>+</sup> regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes ...[more]

PMID: 32321922

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Project description:The notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing β cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.

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

Publications

CD8<sup>+</sup> regulatory T cells are critical in prevention of autoimmune-mediated diabetes.

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

Publications

CD8<sup>+</sup> regulatory T cells are critical in prevention of autoimmune-mediated diabetes.

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OmicsDI is part of the ELIXIR infrastructure

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