Abstract
Calcium is the most abundant mineral in the human body and is central to many physiological processes, including immune system activation and maintenance. Studies continue to reveal the intricacies of calcium signalling within the immune system. Perhaps the most well-understood mechanism of calcium influx into cells is store-operated calcium entry (SOCE), which occurs via calcium release-activated channels (CRACs). SOCE is central to the activation of immune system cells; however, more recent studies have demonstrated the crucial role of other calcium channels, including transient receptor potential (TRP) channels. In this review, we describe the expression and function of TRP channels within the immune system and outline associations with murine models of disease and human conditions. Therefore, highlighting the importance of TRP channels in disease and reviewing potential. The TRP channel family is significant, and its members have a continually growing number of cellular processes. Within the immune system, TRP channels are involved in a diverse range of functions including T and B cell receptor signalling and activation, antigen presentation by dendritic cells, neutrophil and macrophage bactericidal activity, and mast cell degranulation. Not surprisingly, these channels have been linked to many pathological conditions such as inflammatory bowel disease, chronic fatigue syndrome and myalgic encephalomyelitis, atherosclerosis, hypertension and atopy.
Highlights
IntroductionCalcium signalling is important in immune system activation and maintenance. Transient receptor operated (TRP) channels are considered a major source of Ca2+ entry into cells
Highlights Calcium signalling is important in immune system activation and maintenance Transient receptor operated (TRP) channels are considered a major source of Ca2+ entry into cells transient receptor potential (TRP) channels have a diverse subtype and are expressed in most of immune cells TRP channels can respond to heat, pH changes, mechanical cues and result in surge of calcium entry They offer a potential therapeutic target that can be useful in modulation of immune system in conditions such as allergy, transplantation and canceroImmunomodulation is the process which results in regulation or alteration of the scope, type, duration, or competency of an immune response [1]
Stimulation of immune cells results in the depletion of endoplasmic reticulum (ER) C a2+ stores [12]. This seems to be sensed by stromal interaction molecule 1 (STIM1) located within the ER through interaction with plasma proteins, namely Orai1 protein. This results in sustained activation of calcium release-activated channels (CRACs) resulting in calcium influx, a process known as store-operated calcium entry (SOCE)
Summary
Calcium signalling is important in immune system activation and maintenance. Transient receptor operated (TRP) channels are considered a major source of Ca2+ entry into cells. Immunomodulation encompasses any intervention directed at modifying the immune response with a therapeutic end point Such strategies have clinical importance in the development of new vaccines, treatment of autoimmune diseases and allergies, strategies in regenerative medicine, transplantation and immunotherapy for cancer (Fig. 1) [1–5]. This results in sustained activation of calcium release-activated channels (CRACs) resulting in calcium influx, a process known as store-operated calcium entry (SOCE) (reviewed in [13]) Such sustained calcium influx across the cell membrane is important for lymphocyte activation and the initiation of both innate and adaptive immune response [11, 14, 15]. The TRP ion channels are a large and diverse family of proteins with their subunits united by a common primary structure and permeability to monovalent cations and divalent calcium ions (Fig. 2) [17–19] They are involved in a continually growing number of cellular functions [20]. We will highlight future approaches and new treatment options
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