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Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
Published on: October 25, 2024
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Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells
An-Qi Shang1, Chang-Jiang Yu2, Xin Bi1
1Departments of Cardiology and Critical Care Medicine, NHC Key Laboratory of Cell Transplantation, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Summary
Anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody worsens heart failure in mice by promoting T helper 17 (Th17) cell differentiation. Targeting the CXCR4/Th17/IL-17A pathway may prevent immune checkpoint inhibitor cardiotoxicity.
Area of Science:
- Immunology
- Cardiology
- Oncology
Background:
- Immune checkpoint inhibitors like anti-CTLA-4 antibodies offer cancer immunotherapy benefits but can cause cardiac adverse effects.
- Pressure overload models, such as transverse aortic constriction (TAC), induce cardiac remodeling and heart failure.
Purpose of the Study:
- To investigate the impact of anti-CTLA-4 antibody on pressure overload-induced cardiac remodeling and dysfunction.
- To elucidate the underlying mechanisms of anti-CTLA-4 antibody-mediated cardiotoxicity.
Main Methods:
- Mice underwent TAC to induce cardiac hypertrophy and heart failure.
- Anti-CTLA-4 antibody was administered, followed by assessments of cardiac function, histology, and immune cell profiles.
- Interventions included anti-IL-17A antibody and CXCR4 antagonist AMD3100.
Main Results:
- Anti-CTLA-4 antibody exacerbated TAC-induced cardiac dysfunction, hypertrophy, and fibrosis.
- Elevated systemic inflammatory factors and increased T helper 17 (Th17) cell differentiation were observed.
- Inhibition of IL-17A or CXCR4 reversed the cardiotoxic effects.
Conclusions:
- Anti-CTLA-4 antibody administration worsens pressure overload-induced heart failure via Th17 cell activation and differentiation.
- Targeting the CXCR4/Th17/IL-17A axis presents a potential strategy to mitigate cardiotoxicity from immune checkpoint inhibitors.
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