Transient receptor potential ankyrin1 channel is endogenously expressed in T cells and is involved in immune functions.

P. Sanjai Kumar,Subhransu Sekhar Sahoo,Tusar Acharya,Abhishek Kumar,Chandan Goswami,Ankit Tiwari,Somdatta Saha,Subhasis Chattopadhyay,Rakesh Kumar Majhi

doi:10.1042/bsr20191437

Abstract

Transient receptor potential channel subfamily A member 1 (TRPA1) is a non-selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the information on the role of TRPA1 toward T-cell responses remains scanty. In silico data suggest that TRPA1 can play an important role in the T-cell activation process. In this work, we explored the endogenous expression of TRPA1 and its function in T cells. By reverse transcription polymerase chain reaction (RT-PCR), confocal microscopy and flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. TRPA1 is primarily located at the cell surface. TRPA1-specific activator namely allyl isothiocyanate (AITC) increases intracellular calcium ion (Ca2+) levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+ levels in T cells; TRPA1 inhibition also reduces TCR-mediated calcium influx. TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or Concanavalin A (ConA)-driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of cluster of differentiation 25 (CD25), cluster of differentiation 69 (CD69) in ConA/TCR stimulated T cells and secretion of cytokines like tumor necrosis factor (TNF), interferon γ (IFN-γ), and interleukin 2 (IL-2) suggesting that endogenous activity of TRPA1 may be involved in T-cell activation. Collectively these results may have implication in T cell-mediated responses and indicate possible role of TRPA1 in immunological disorders.

Highlights

Transient receptor potential cation channel subfamily A member 1 (TRPA1) is the only member of the mammalian ‘ankyrin’ type subfamily of TRP channels [1]
By reverse transcription polymerase chain reaction (RT-PCR), confocal microscopy and flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells
TRPA1 gene input was made into Search Tool for the Retrieval of Interacting Genes/Proteins (STRING 10) [14] web tool for exploring protein–protein interactions with the confidence score higher than 0.7 with the top interacting partners; Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology annotations were deduced for TRPA1 interacting partners using g:profiler webserver [15]

Summary

Introduction

Transient receptor potential cation channel subfamily A member 1 (TRPA1) is the only member of the mammalian ‘ankyrin’ type subfamily of TRP channels [1]. TRPA1 is a calcium ion (Ca2+)-permeable non-selective cation channel that is expressed in a set of nociceptive/thermo-receptive neurons that can detect noxious cold temperatures below 17◦C. It is often co-expressed with the heat-sensitive channel, transient receptor potential cation channel subfamily transient receptor potential vanilloid (TRPV1) rather than with the cold-sensitive channel TRPM8. Apart from low temperature as a stimulus, TRPA1 acts as a nociceptive receptor that detects noxious chemicals that can cause tissue damage. TRPA1 acts as a mediator of inflammatory pain generated by either noxious cold or chemical irritants [4,5]

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