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05.10.2017 | Original Article

Human amylin induces CD4+Foxp3+ regulatory T cells in the protection from autoimmune diabetes

verfasst von: Xiao-xi Zhang, Yong-chao Qiao, Wan Li, Xia Zou, Yin-ling Chen, Jian Shen, Qin-yuan Liao, Qiu-jin Zhang, Lan He, Hai-lu Zhao

Erschienen in: Immunologic Research | Ausgabe 1/2018

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Abstract

Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet β cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic β cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9-fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-β (TGF-β) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions.

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Titel: Human amylin induces CD4+Foxp3+ regulatory T cells in the protection from autoimmune diabetes
verfasst von: Xiao-xi Zhang
Yong-chao Qiao
Wan Li
Xia Zou
Yin-ling Chen
Jian Shen
Qin-yuan Liao
Qiu-jin Zhang
Lan He
Hai-lu Zhao
Publikationsdatum: 05.10.2017
Verlag: Springer US
Erschienen in: Immunologic Research / Ausgabe 1/2018
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-017-8956-5

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Human amylin induces CD4+Foxp3+ regulatory T cells in the protection from autoimmune diabetes

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