IL-35 improves Treg-mediated immune suppression in atherosclerotic mice

Tao,Linlin; Zhu,Jie; Chen,Yuefeng; Wang,Qinghang; Pan,Ying; Yu,Qianqian; Zhou,Birong; Zhu,Huaqing

doi:10.3892/etm.2016.3649

IL-35 improves Treg-mediated immune suppression in atherosclerotic mice

Authors:
- Linlin Tao
- Jie Zhu
- Yuefeng Chen
- Qinghang Wang
- Ying Pan
- Qianqian Yu
- Birong Zhou
- Huaqing Zhu
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Affiliations: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Anhui 230601, P.R. China, Laboratory of Molecular Biology and Department of Biochemistry, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: September 1, 2016 https://doi.org/10.3892/etm.2016.3649
Pages: 2469-2476
Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interleukin (IL)-35 is an anti‑inflammatory cytokine that may have a protective role in atherosclerosis (AS). However, the exact role of IL-35 in the disease, and the etiology of AS, remain incompletely understood. The present study aimed to investigate whether exogenous IL‑35 was able to attenuate the formation of atherosclerotic lesions in apoE‑/‑ mice, and analyze alterations in the expression levels of forkhead box protein 3 (Foxp3) in peripheral blood and the lesions during the progression of AS. ApoE‑/‑ mice were randomly divided into two groups that received either a basal diet (negative control group) or a high‑fat diet (HFD) for 4 weeks. The HFD group was further subdivided into groups that received IL‑35, atorvastatin or no treatment for 12 weeks. Diagnostic enzyme assay kits were applied for the detection of plasma lipids, and hematoxylin and eosin staining was used to analyze the severity of atherosclerotic lesions in apoE‑/‑ mice. Immunohistochemistry and flow cytometry were performed to analyze the expression of Foxp3 in the plasma and atherosclerotic plaques. As compared with the negative control group, the plasma lipids were significantly increased, and the lesions were obviously formed, in the HFD groups. Furthermore, the area of the lesion was reduced in IL‑35- and atorvastatin‑treated groups, as compared with the AS control group. In addition, Foxp3 expression was upregulated in the plasma and lesions of the IL‑35‑ and atorvastatin‑treated groups, as compared with the AS control group. The present study demonstrated that IL‑35 improved Treg-mediated immune suppression in atherosclerotic mice, thus suggesting that IL‑35 may be a novel therapeutic target for AS.

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