Effect of boswellic acids on the expression of PD-1 and TIGIT immune checkpoints on activated human T cells.

Meyiah, Abdo; Al-Harrasi, Ahmed; Ur Rehman, Najeeb; Elkord, Eyad

Abstract

Boswellic acids (BAs) have been documented as anti-inflammatory agents with the potential to regulate immune responses. However, their impacts on the expression level of immune checkpoint (IC) molecules in T cells have never been reported. By using flow cytometric assays, we investigated whether BAs extracted from Boswellia sacra (B. sacra) have any potential effects on the expression of PD-1 and TIGIT immune checkpoints (ICs) on activated T cells in vitro. Interestingly β-BA at a concentration of 50 μM significantly reduced the expression of PD-1 and TIGIT on both activated CD4 and CD8 T cells without any cytotoxicity. Additionally, β-KBA significantly reduced the percentages of CD4 PD-1 and CD8 TIGIT T cells at 50 μM concentration. Furthermore, a significant reduction in CD4 PD-1 T cells was observed following treatment with a lower concentration (25 μM) of β-AKBA. These findings show that BA compounds have the ability to reduce the expression of PD-1 and TIGIT in stimulated human T cells, which might play critical roles in reinvigorating exhausted T cells, indicating their potentials in immunosuppressed disease settings such as cancers and infections. This study is the first to investigate the effects of these compounds on the expression of immune checkpoints in human T cells. Clearly, further investigations are required to assess the mechanism of action of these compounds on ICs, and their efficacy as therapeutic agents in different diseases.

• Journal Article Type: Article
• Acceptance Date: Feb 1, 2025
• Online Publication Date: Feb 3, 2025
• Publication Date: 2025-03
• Deposit Date: May 15, 2025
• Journal: Fitoterapia
• Print ISSN: 0367-326X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 181
• Article Number: 106401
• DOI: https://doi.org/10.1016/j.fitote.2025.106401
• Keywords: Immune checkpoint receptors, Boswellic acids, Receptors, Immunologic, Programmed Cell Death 1 Receptor, Boswellia - chemistry, PD-1, Humans, CD8-Positive T-Lymphocytes - drug effects, T cells, TIGIT, Lymphocyte Activation - drug effects, Triterpenes - pharmacology, CD4-Positive T-Lymphocytes - drug effects