Interleukin-27 and Interleukin-2 Cooperatively Regulate CD4⁺ T Cell Subsets and Immune Imbalance in Coronary Artery Disease

  • J Inflamm Res. 2025 Dec 10:18:17253-17269. doi: 10.2147/JIR.S545568.
Yifan Cai  #  1  2  3 ,  Hongxia Tang  #  4 ,  Wenwen Tang  #  5 ,  Wenjuan Tang  6 ,  Wenbin Xu  1  2  3 ,  Yue Wang  1  2  3 ,  Yan Ding  1  2  3 ,  Jian Yu  1  2  3 ,  Chengliang Pan  1  2  3 ,  Zhiyang Li  1  2  3 ,  Yudong Peng  1  2  3 ,  Ruirui Zhu  1  2  3 ,  Kunwu Yu  1  2  3 ,  Qiutang Zeng  1  2  3 ,  Yucheng Zhong  7
Affiliations
  • 1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • 2. Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • 3. Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • 4. Department of Rheumatology and Immunology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, People's Republic of China.
  • 5. Cardiovascular Department, Wuhan No.9 Hospital, Wuhan, Hubei, People's Republic of China.
  • 6. Radiology Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • 7. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
  • # Contributed equally.
PMID: 41399529 DOI: 10.2147/JIR.S545568
Abstract

Background: Coronary artery disease (CAD) is an immune-mediated disorder driven by dysregulated T cell responses. Interleukin-27 (IL-27) has immunoregulatory properties, but its role in CAD remains unclear. This study is the first to investigate the effects of IL-27 on CD4⁺LAP⁺ T cells in CAD and to explore its interaction with interleukin-2 (IL-2) in modulating immune imbalance.

Methods: CAD severity was quantified by the Gensini score. Plasma IL-27 and oxidized low-density lipoprotein (ox-LDL) were measured by ELISA. Flow cytometry assessed CD4⁺ T cell subsets, while qRT-PCR and Western blot evaluated lineage-specific transcription factors.

Results: IL-27 levels were elevated in acute coronary syndrome and correlated with ox-LDL and Gensini scores. Patients with severe CAD showed a Th1/Th17-dominant profile and reductions in Th2, CD4⁺LAP⁺, and Tregs. In vitro, IL-27 promoted Th1 differentiation via T-bet/IFN-γ upregulation and suppressed Th2, Th17, and regulatory subsets, counteracting IL-2-induced expansion of Tregs and CD4⁺LAP⁺ cells. These effects were dose dependent and favored pro-inflammatory responses.

Conclusion: IL-27 drives immune imbalance in CAD by reinforcing Th1 polarization and antagonizing IL-2-mediated regulation. Beyond mechanistic insights, these findings identify IL-27 as a potential biomarker for disease severity and a candidate therapeutic target in CAD.

Keywords
IL-27; Th1/Th2; Th17/CD4+LAP+ T cells; coronary artery disease.
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