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. 2022 Sep;13(9):1489-1495.
doi: 10.1111/jdi.13829. Epub 2022 May 26.

Combination of anti-CD25 antibody and poly I:C treatment in pregnant NOD mice may be used as 'pregnancy-related' type 1 diabetes model

Akira Shimada  1 , Kyoko Toda  1 , Ikuo Inoue  1 , Taketo Yamada  2 , Yoichi Oikawa  1
Affiliations

Combination of anti-CD25 antibody and poly I:C treatment in pregnant NOD mice may be used as 'pregnancy-related' type 1 diabetes model

Akira Shimada et al. J Diabetes Investig. 2022 Sep.

Abstract

Aims/introduction: Some women develop type 1 diabetes during pregnancy or immediately after delivery. However, the underlying pathophysiology remains largely unknown, probably because of the lack of a suitable animal model. In this study, we administered pregnant NOD mice with an anti-CD25 antibody to reduce regulatory T cells along with poly I:C and examined the onset of diabetes.

Materials and methods: Anti-CD25 antibody and poly I:C were intraperitoneally administered to mated female NOD mice. Mice delivered within 3 weeks after the treatment, and the onset of diabetes during pregnancy or within 6 weeks after delivery was examined. Some mice were killed 1 week after treatment, and their spleen and pancreas were excised to examine the expression levels of cytokines and for histological examination.

Results: Half of the mice treated with anti-CD25 antibody plus poly I:C developed diabetes, as compared with none of the poly I:C-injected mice (P < 0.05). The ratios of interleukin-18/forkhead box P3 and granzyme B/forkhead box P3 were higher in the pancreas of anti-CD25 antibody plus poly I:C-treated mice than in the pancreas of control mice. The insulitis score decreased in the pancreas of anti-CD25 antibody plus poly I:C-injected pregnant NOD mice.

Conclusions: We describe the use of anti-CD25 antibody to reduce regulatory T cells and poly I:C as a Toll-like receptor 3 stimulator to mimic viral infection in a pregnant NOD mouse, which can be used as a model of 'pregnancy-related' type 1 diabetes.

Keywords: NOD mouse; Pregnancy; Type 1 diabetes.

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Figures

Figure 1
Figure 1
Diabetes incidence in treated pregnant NOD mice. Solid line: anti‐CD25 antibody + poly I:C injection group (n = 14); dotted line: poly I:C‐only injection group (n = 9). *P < 0.05. [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Interleukin (IL)‐18/forkhead box P3 (Foxp3) and granzyme B/Foxp3 ratios in the pancreas of treated pregnant NOD mice. Closed bar: anti‐CD25 antibody + poly I:C injection group (n = 5); open bar: poly I:C only injection group (n = 5). *P < 0.05.
Figure 3
Figure 3
Lower insulitis score observed in the pancreas of anti‐CD25 antibody plus poly I:C‐injected pregnant NOD mice. *P < 0.05.
See this image and copyright information in PMC

References

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