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Increased Th9 cells and IL-9 levels accelerate disease progression in experimental atherosclerosis
Qing Li1, Tingting Ming1, Yuanmin Wang2
1The Central Laboratory of Medical Research Center, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, Anhui, PR China.
Insights
This study reveals that Th9 cells and IL-9 significantly contribute to atherosclerosis development. Targeting these elements with antibodies may offer a new therapeutic strategy for this chronic inflammatory disease.
Area of Science:
- Immunology
- Cardiovascular Research
- Inflammation Biology
Background:
- Atherosclerosis (AS) is a leading cause of death globally, recognized as a chronic inflammatory condition.
- T cells are implicated in AS pathogenesis, but the role of the Th9 subset remains unclear.
Purpose of the Study:
- To investigate the role of Th9 cells and their associated cytokine, IL-9, in the development of atherosclerosis.
- To assess Th9 cell populations, IL-9 levels, and the transcription factor PU.1 in a mouse model of AS.
Main Methods:
- Quantification of Th9 cells, IL-9, and PU.1 in ApoE-/- mice (prone to atherosclerosis) versus C57BL/6J mice.
- Administration of recombinant IL-9 (rIL-9) to assess its effect on AS progression.
- Treatment with anti-IL-9 antibodies to evaluate therapeutic potential.
Main Results:
- ApoE-/- mice exhibited significantly higher numbers of Th9 cells, elevated IL-9 levels, and increased PU.1 expression compared to control mice.
- Exogenous rIL-9 exacerbated atherosclerotic lesion development.
- Anti-IL-9 antibody treatment attenuated the progression of atherosclerosis.
Conclusions:
- Th9 cells and IL-9 play a critical role in promoting the pathogenesis of atherosclerosis.
- Targeting Th9 cells and IL-9 via antibody-based therapies presents a promising novel therapeutic avenue for AS treatment.
Abstract:
Atherosclerosis (AS) is the number one killer in developed countries, and currently considered a chronic inflammatory disease. The central role of T cells in the pathogenesis of atherosclerosis is well documented. However, little is known about the newly described T cell subset-Th9 cells and their role in AS pathogenesis. Here, the amounts of Th9 cells as well as their key transcription factors and relevant cytokines during atherosclerosis were assessed in ApoE-/- mice and age-matched C57BL/6J mice. Significantly increased Th9 cell number, Th9 related cytokine (IL-9), and key transcription factor (PU.1) were found in ApoE-/- mice compared with age-matched C57BL/6J mice. Additionally, treatment with rIL-9 accelerated atherosclerotic development, which was attenuated by anti-IL-9 antibodies. These data suggested that both Th9 cells and related IL-9 play key roles in the pathogenesis of atherosclerosis, and antibodies against these antigens offer a novel therapeutic approach in AS treatment.