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IL-17 affects the immune regulation of CD4+ T cells in dilated cardiomyopathy through JAK/STAT pathway

Published online by Cambridge University Press:  06 January 2025

Jie Hao Open the ORCID record for Jie Hao [Opens in a new window] ,
Weiwei Li ,
Wei Jiao ,
Fang Li  and
Yanan Xie
Jie Hao*
Affiliation:
Department of Cardiovascular, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Weiwei Li
Affiliation:
Department of Cardiovascular, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Wei Jiao
Affiliation:
Department of Cardiovascular, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Fang Li
Affiliation:
Department of Cardiovascular, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Yanan Xie
Affiliation:
Department of Cardiovascular, The Second Hospital of Hebei Medical University, Shijiazhuang, China
*
Corresponding author: Jie Hao; Email: haojiemed@hebmu.edu.cn
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Abstract

Purpose:

Studying the effect of interleukin-17 (IL-17) on the mechanism of CD4+ T-cell immune regulation and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway may offer new ideas and methods for the therapy of dilated cardiomyopathy.

Methods:

Naive CD4+ T cells were isolated from mice using a magnetic bead sorting reagent and manipulated by overexpression or knockdown of IL-17. Protein levels of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p-STAT3), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were determined by Western blotting. Quantitative polymerase chain reaction was used to assess the levels of JAK2, STAT3, MMP-2, and MMP-9. Expression of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-4 (IL-4), and interferon-gamma (IFNγ) was determined by enzyme-linked immunosorbent assay test kits. TNF-α, IL-1β, IL-4, and IFNγ secretion was measured by flow cytometry.

Results:

In CD4+ T cells, IL-17 overexpression increased TNF-α, IL-1β, IL-4, IFNγ, p-JAK2, p-STAT3, MMP-2, MMP-9 levels, and apoptosis. Knockdown of IL-17 reduced the levels of TNF-α, IL-1β, IL-4, IFNγ, p-JAK2, p-STAT3, MMP-2, and MMP-9, as well as the level of apoptosis.

Conclusion:

Through regulation of IL-17 expression in CD4+ T cells, this study reveals its crucial role in regulating the secretion of inflammatory factors, activation of the JAK/STAT signaling pathway, expression of matrix metalloproteinases, and apoptosis of CD4+ T cells.

Keywords

IL-17JAK/STATCD4+Tdilated cardiomyopathy
Type
Original Article
Information
Cardiology in the Young , Volume 35 , Issue 1 , January 2025 , pp. 16 - 23
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Copyright
© The Author(s), 2025. Published by Cambridge University Press

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