The role of transient receptor potential vanilloid type-2 ion channels in innate and adaptive immune responses

Abstract

The transient receptor potential vanilloid type-2 (TRPV2), belonging to the transient receptor potential channel family, is a specialized ion channel expressed in human and other mammalian immune cells. This channel has been found to be expressed in CD34+ hematopoietic stem cells, where its cytosolic Ca2+ activity is crucial for stem/progenitor cell cycle progression, growth, and differentiation. In innate immune cells, TRPV2 is expressed in granulocytes, macrophages, and monocytes where it stimulates fMet-Leu-Phe migration, zymosan-, immunoglobulin G-, and complement-mediated phagocytosis, and lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-6 production. In mast cells, activation of TRPV2 allows intracellular Ca2+ ions flux, thus stimulating protein kinase A-dependent degranulation. In addition, TRPV2 is highly expressed in CD56+ natural killer cells. TRPV2 orchestrates Ca2+ signal in T cell activation, proliferation, and effector functions. Moreover, messenger RNA for TRPV2 are expressed in CD4+ and CD8+ T lymphocytes. Finally, TRPV2 is expressed in CD19+ B lymphocytes where it regulates Ca2+ release during B cell development and activation. Overall, the specific expression of TRPV2 in immune cells suggests a role in immune-mediated diseases and offers new potential targets for immunomodulation.

Silver Nanoparticle-Directed Mast Cell Degranulation Is Mediated through Calcium and PI3K Signaling Independent of the High Affinity IgE Receptor

“…Several inhibitors have been shown to block CRAC channels such as SKF-96365 and Synta (compound 66, GSK1349571A), with the later lacking any effects on inwardly rectifying K + channels or plasma membrane calcium ATPase pump at a concentration of 10 μM [25]. Our data show that pre-treatment with Synta resulted in only a partial inhibition of AgNP-induced mast cell degranulation suggesting that other calcium channels might be involved in mediating calcium influx in response to AgNP exposure such as vanilloid receptor–related transient receptor potential (TRPV) that has been previously shown to mediate calcium influx during mast cell degranulation [70]. Synta by itself induced degranulation of mast cells which was not due to cell toxicity.…”

Tranilast: A review of its therapeutic applications

“…TRPV2 plays a role in mast cell degranulation [186], possibly explaining the beneficial effects of tranilast in allergic disorders. It has a specific expression in immune cells that suggests a role in immune-mediated disorders [187], and since tranilast is effective in immune system diseases, perhaps some of these effects are related to TRPV2. It also appears to be important in the endocrine system, more specifically in pancreas and insulin secretion.…”

TRP Channels in Skin Biology and Pathophysiology

“…TRPV2 expression has been reported in a range of immune/inflammatory cell types, including macrophages, mast cells, natural killer cells, dendritic cells and lymphocytes [85]. Within these cell types, TRPV2 has been implicated in regulating diverse functions that include cytokine release [86], chemotaxis [87,88], phagocytosis [87], endocytosis [89], inflammasome activity [90], and podosome assembly [91].…”