Deciphering the Role of Endolysosomal Ca2+ Channels in Immunity

Abstract

The role of endolysosomal Ca2+ signalling in immunity has been a subject of increasing interest in recent years. Here, we discuss evolving knowledge relating to the contribution of endolysosomal Ca2+ channels that include TPCs, TRPMLs, and P2X4R in physiological processes related to innate and adaptive immunity—including phagocytosis, inflammation, cytokine/chemokine release, dendritic, natural killer, and T cell activation and migration—and we underscore the paucity of clinical studies in this field. Emerging biomedical and translational data have led to important new insights into the critical roles of these channels in immune cell function and the regulation of innate and adaptive immune responses. The evolving immunological significance of endolysosomal Ca2+ signalling warrants further investigations to better characterize the roles of these channels in immunity in order to expand our knowledge about the pathology of inflammatory and autoimmune diseases and develop endolysosomal Ca2+ channels as viable biomarkers and therapeutic and preventive targets for remodelling the immune response.

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8+ T‐Cell Response

“…Homeostasis of Ca 2+ , which is an important secondary messenger, is essential for DC migration as it controls the phosphorylation of a variety of signaling proteins such as Rac1, Cdc42, and PKC upstream of cytoskeletal components, including F‐actin and focal adhesion. [ 31 ] To play this role, intracellular Ca 2+ must be tightly regulated; Ca 2+ pulses and spikes should occur at the right place and time, selectively activating numerous downstream signaling targets. [ 32 ] Before testing whether Lap acts on Ca 2+ homeostasis, we characterized the process of Lap entering DCs to capture Lap‐induced Ca 2+ transients.…”

“…In summary, once Lap is incapacitated to generate radicals, it loses the ability to induce lysosomal stress, accompanied by the loss of Ca 2+ mobilization, and finally decrease of Lap‐induced DC homing, suggesting a novel regulatory axis of Lap‐induced lysosomal reprogramming, Ca 2+ mobilization, and DC migration. [ 31 , 32 ] Recently, several studies have designed nanovaccines targeting Ca 2+ ‐related specific immune activation. However, most of these are calcium‐based nanomaterials (e.g., CaP, CaO 2 , CaCO 3 , and Ca 10 (PO 4 ) 6 (OH) 2 ) with the objective of introducing exogenous Ca 2+ .…”

Ca2+-Dependent Processes of Innate Immunity in IBD

“…Monocytes, macrophages, dendritic cells, mast cells, basophils, neutrophils, eosinophils, and natural killer cells comprise the innate immune system, whereas B and T cells comprise the adaptive immune system [22]. Ca 2+ signalling is required for the maintenance of several immune cell functions, and different investigations have discovered that Ca 2+ dysregulation is connected to the development of autoimmune and inflammatory disorders [19]. Figure 1 show the mechanisms of innate immunity cell involved in IBD pathogenesis.…”

“…Ca 2+ signalling plays a critical role in regulating a wide array of immune cell functions, many of which are implicated in the pathogenesis of IBD [10]. In particular, calcium ions (Ca 2+ ) act as key messengers within T cells, macrophages, and neutrophils, orchestrating processes such as leukocyte adhesion, migration, activation, cytokine production, and cell survival [19,20]. Dysregulation of these calcium-dependent processes in IBD can modulate the production of pro-inflammatory cytokines and the migration of immune cells to the gut.…”

“…Considering that Ca 2+ signals play a crucial role in immune system function [19,20], such as in cytokine and chemokines secretion, in this review, we discuss the potential involvement of immune cells and their Ca 2+ -dependent processes in IBD pathogenesis and the possibility to modulate this signalling as a therapeutic avenue.…”