TRP Channels in Inflammation and Immunity

About this Research Topic

Background

Transient receptor potential (TRP) ion channels regulate multiple cellular mechanisms that are relevant for the physiological homeostasis of hematopoietic cells. Because TRP cation channels are Ca²⁺-permeable, they have emerged as key functional elements for the control of calcium signals and ionic balances in immune cells. During inflammation and the onset of immune responses, immune cells exert broad essential cellular processes including activation and proliferation, migration, phagocytosis, and cytokine production. Over the past few years, novel findings on TRP channels indicate these cellular sensors modulate many of the effector functions in immune cells.

The precise understanding of the complex interaction of Ca²⁺ and diverse cytosolic proteins in non-excitable cells continues to be a challenge. In resting immune cells, a functionally coupled network of membrane transporters, ion channels, and calcium binding proteins maintains the cytosolic calcium concentration in the nanomolar range. The resting state of the cells, however, can be perturbed by the ion channel activity linked to plasma membrane receptor-ligand interaction. Activation of immune cells often induces pronounced changes of the membrane potential and the release of Ca²⁺ from intracellular stores such as the endoplasmic reticulum (ER). The drop in ER luminal Ca²⁺ concentration is followed by the opening of plasma membrane channels leading to further elevation of intracellular levels of Ca²⁺, which ensures adequate Ca²⁺-dependent effector functions in immune cells. In addition, Ca²⁺ release from other intracellular organelles, such as the endo-lysosomal compartment harboring organelle specific TRP channels, is essential to shaping characteristic Ca²⁺ signals in immune cells.

TRP channels respond to a variety of chemical and physical stimuli derived from harmful agents, and contribute to increased intracellular cation concentrations. TRP channel-mediated effects in immune cells are diverse and range from regulation of cell migration and phagocytosis, to the production and release of inflammatory mediators. Furthermore, these channels mediate an active cross-talk between epithelial cells, neuronal tissue, and the immune cells that orchestrate immune responses to tissue damage or infection. Because of the wide functional role of TRP channels in inflammation and immunity, the use of specific agonists or antagonists becomes an amenable pharmacological tool in an effort to develop novel treatments for infectious and inflammatory diseases and cancer.

This Research Topic will provide a comprehensive overview of how TRP channels modulate the function of innate immune cells during physiological and immunopathological responses. This collection will further support the development of the nascent interdisciplinary field of immunophysiology and will recognize the potential of TRP channels as therapeutic targets. We welcome original research articles and reviews that cover, but are not limited to, the following research areas:

1. TRP channel expression and function in immune cells
2. Mechanisms of TRP channel activation and their impact on immune cell function
3. The roles of TRP channels during inflammation and host defense
4. Research models for the study of TRP channels and innate immunity
5. Clinical and translational studies related to TRP channels and immune cells
6. Current developments in TRP channels as immunotherapeutic targets

Keywords: Ion channels, calcium signaling, phagocytes, monocytes, neutrophils

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