A study published in Nature Immunology reveals a previously unrecognized, ‘non-canonical’ role of the pain TRPV1 receptor – namely, its functional expression, and involvement in TCR signaling and pro-inflammatory activities of T cells.
Transient receptor potential vanilloid type 1 ion channel (TRPV1), initially identified as the receptor for capsaicin (the hot ingredient of chilli peppers) belongs to the family of nociceptors (pain receptors).
It is mostly expressed in sensory neurons and responds to noxious stimuli such as heat (>42 C°), protons and vanilloids such as capsaicin or allyl isothiocyanate, the pungent compound in mustard and wasabi. TRPV1 also contributes to the development of burning pain and reflex hyperactivity associated with inflammation of peripheral tissues and viscera (Nagy I et al., Prog Drug Res, 2014, 68:39).
In the central nervous system, new research indicates that TRPV1 contributes to fear, anxiety, stress, thermoregulation, pain, and synaptic plasticity (Edwards JG., Prog Drug Res, 2014, 68:77). Of note, TRPV1 also plays a key role in acid sensing by sensory neurons in inflammation and related diseases.
In the Nature Immunology study, Samuel Bertin and colleagues, as part of an international research team from the US, Japan, Canada and China found that the TRPV1 was constitutively expressed in mouse and human CD4+ T cells, and the Jurkat human leukemic T cell line.
The whole-cell patch clamp demonstrated the functionality of the TRPV1 channel at the plasma membrane, recording capsaicin-induced currents in CD4+ T cells.
The authors provided evidence that TRPV1 is a functional Ca2+channel, contributing to TCR-induced Ca2+ influx. Importantly, they showed that it was necessary for proper downstream TCR-induced signaling and cytokine production, such as IFN-γ, IL-17A and TNF, and the T cell inflammatory responses in vivo in two models of inflammatory bowel disease.
In addition, the authors demonstrated that TRPV1 antagonists expressed immune-modulatory properties; they suggest that their application may prove beneficial in immune- and T cell-related diseases such as inflammatory bowel disease.
Source: Nat Immunol, 2014, 11:1055. doi: 10.1038/ni.3009. Epub 2014 Oct 5.
Read more: Nature Immunology