SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155

Li Li; Wenqi Shan; Haijin Zhu; Fei Xue; Yongbin Ma; Liyang Dong; Dingqi Feng; Jiahui Mao; Guoyue Yuan; Xuefeng Wang

doi:10.2147/JIR.S334636

SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155

J Inflamm Res. 2021 Oct 14:14:5305-5318. doi: 10.2147/JIR.S334636. eCollection 2021.

Authors

Li Li^#^{1

2}, Wenqi Shan^#^{1

3}, Haijin Zhu^#^{1

3}, Fei Xue^{1

2}, Yongbin Ma^{1

4}, Liyang Dong^{1

5}, Dingqi Feng¹, Jiahui Mao¹, Guoyue Yuan⁶, Xuefeng Wang^{1

5}

Affiliations

¹ Department of Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People's Republic of China.
² Department of Clinical Laboratory, The Taixing City People's Hospital, Taixing, 225400, People's Republic of China.
³ Department of Pediatrics, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People's Republic of China.
⁴ Department of Central Laboratory, Jintan Hospital, Jiangsu University, Jintan, 213200, People's Republic of China.
⁵ Department of Nuclear Medicine and Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People's Republic of China.
⁶ Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Helminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma. We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice. This study mainly investigated the molecular mechanism of SJMHE1 in inhibiting asthma inflammation.

Methods: SJMHE1 was administered to mice with OVA-induced asthma via subcutaneous injection, and its effects were detected by testing the airway inflammation of mice. The Th cell distribution was analyzed by flow cytometry. Th-related transcription factor and cytokine expression in the lungs of mice were analyzed using quantitative real-time PCR (qRT-PCR). The expression of miR-155 and levels of phosphorylated STAT3 and STAT5 were also determined after SJMHE1 treatment in mice by qRT-PCR and Western blot analysis. The in vitro mouse CD4⁺ T cells were transfected with lentivirus containing overexpressed or inhibited miR-155, and the proportion of Th17, Treg cells, CD4⁺p-STAT3⁺, and CD4⁺p-STAT5⁺ cells were analyzed by flow cytometry.

Results: SJMHE1 ameliorated the airway inflammation of asthmatic mice, upregulated the proportion of Th1 and Treg cells, and the expression of Th1 and Treg-related transcription factor and cytokines. Simultaneously, SJMHE1 treatment reduced the percentage of Th2 and Th17 cells and the expression of Th2 and Th17-related transcription factor and cytokines. SJMHE1 treatment decreased the expression of miR-155 and p-STAT3 but increased p-STAT5 expression. In vitro, the percentage of Th17 and CD4⁺p-STAT3⁺ cells increased in CD4⁺ T cells transfected over-expression of miR-155, but SJMHE1 inhibited the miR-155-mediated increase of Th17 cells. Furthermore, SJMHE1 increased the proportion of Treg and CD4⁺p-STAT5⁺ cells after transfected over-expression or inhibition of miR-155.

Conclusion: SJMHE1 regulated the balance of Th17 and Treg cells by modulating the activation of STAT3 and STAT5 via miR-155 in asthma. SJMHE1 might be a promising treatment for asthma.

Keywords: SJMHE1; Schistosoma japonicum peptide; Th17/Treg cell balance; asthma; miR-155.

Grants and funding

This work was supported by a grant from the National Natural Science Foundation of China (81871243 and 81900562), the key research and development programs of Jiangsu Province (BE2017697), the Six Talent Peaks of Jiangsu Province (WSN-009), “LiuGeYi” Projects of Jiangsu Province (LGY2016055), “XueDiJiFang” Projects of Jiangsu Province (x201812), and the Affiliated Hospital of Jiangsu University (jdfyRC2015010).