Upregulation, Functional Association, and Correlated Expressions of TRPV1 and TRPA1 During Telmisartan-Driven Immunosuppression of T Cells

ABSTRACT

TRPV1 and TRPA1, are known to be functionally expressed in T cells, where these two channels differentially regulate effector immune responses. Telmisartan (TM), an anti-hypertension drug, has been recently repurposed to suppress various inflammatory responses. However, the possible involvement of TRP channels during TM-driven suppression of T cells responses has not been explored yet. In this study, we investigated the potential role of TRPV1 and TRPA1 during TM-driven immunosuppression of T cells in vitro. We observed a significant elevation of both TRPV1 and TRPA1 during TM-induced immunosuppression of T cells.We found that TRPA1 activation-driven suppression of T cell activation and effector cytokine responses during TM treatment is partially, yet significantly overridden by TRPV1 activation. Moreover, the expressions of TRPV1 and TRPA1 were highly correlated in various conditions of T cell. Mechanistically, it might be suggested that TRPV1 and TRPA1 are differentially involved in regulating T cell activation despite the co-elevation of both these TRP channels’ expressions in the presence of TM. T cell activation was delineated by CD69 and CD25 expressions along with the effector cytokine levels (IFN-γ and TNF) in TM-driven suppression of T cell. These findings could have broad implications for designing possible future immunotherapeutic strategies, especially in the repurposing of TM for T cell-TRP-directed immune disorders.

KEYWORDS:

• Immune markers
• immunosuppression
• surface expression
• T cell
• telmisartan
• TRPA1
• TRPV1

Acknowledgments

We are thankful to the Animal House and Flow Cytometry Facility of NISER (partially supported by DST-FIST, India) for their support.We are thankful to Dr. Sunil K. Malonia, Molecular and Cancer Biology, UMass Chan Medical School, MA, USA for his suggestions to improve the manuscript. We are highly obliged to Dr. Karl Simin, UMass Chan Medical School, MA, USA for his kind support and critical evaluations towards editing the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization: Tathagata Mukherjee, Chandan Goswami, and Subhasis Chattopadhyay; Methodology: Tathagata Mukherjee, Shyama SubhadarsiniTung, Parthasarathi Jena; Formal analysis and investigation: Tathagata Mukherjee, Chandan Goswami, and SubhasisChattopadhyay; Writing/original draft preparation: Tathagata Mukherjee, Chandan Goswami, and SubhasisChattopadhyay.

Data availability statement

Data supporting the findings of the study are available from the corresponding author upon reasonable request.

Ethical approval

All protocols used for animal (mice) experiments (Protocol no. AH-274) were approved by the IAEC, NISER. This study does not contain any human participants.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2024.2329203

Additional information

Funding

The study was supported by the intramural funding of NISER, Bhubaneswar, Department of Atomic Energy (DAE), Government of India. The funding body has no role in the study design, data collection, data analysis, interpretation of data, writing the manuscript, or decision to publish.