T Cell Ca2+ Signal Dynamics: An Emerging Landscape for Therapeutic Strategies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 51

Special Issue Editors


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Guest Editor
Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA
Interests: calcium signaling; SERCA regulation; T cell signaling; ER calcium stores; Ca2+ release

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Guest Editor
Institute for Neuroimmunology and Multiple Sclerosis Research, Göttingen, Germany
Interests: blood-brain barrier; immune cells; multiple sclerosis; experimental autoimmune encephalomyelitis; two-photon microscopy; B cells; T cells; Dendritic cells; macrophages; astrocytes; microglia; oligodendrocytes; neurons; central nervous system; autoimmune disease; ion channels; calcium signaling
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Special Issue Information

Dear Colleagues,

T lymphocytes have evolved a considerable reliance on the induction and management of the intracellar Ca2+ signal. The foundation of the adaptive immune response is critically dependent on the T cell’s recognition of an antigen and the immediate transduction of antigen recognition via the T cell receptor’s recruitment of a multiplex Ca2+ signal. T cell-activated Ca2+ signals then proceed according to a complex trajectory, with an initial increase in cytoplasmic Ca2+ due to inositol 1,4,5-trisphosphate-mediated release from internal Ca2+ stores, followed by a Ca2+ influx phase due to the activation of plasma membrane-localized Orai Ca2+ channels gated by ER Ca2+ store depletion signals. Importantly, in the absence of the successful deployment of the Ca2+ influx signal, which can occur over protracted periods of T cell engagement with antigen-presenting cells, T cells fail to be adequately activated, resulting in impaired immune function. Thus, there are several key points where the regulation of the T cell Ca2+ signal is important, from the management of ER Ca2+ store status to pathways linked to PM Ca2+ channel activation, all of which warrant closer examination. This could allow us to achieve greater clarity regarding their complex roles and to identify novel targets for therapeutic intervention in cases of immune dysfunction. These topics represent key domains in T cell signaling investigations. This Special Issue will provide a platform for sharing important contributions to this rapidly advancing field in T cell signaling science.

Dr. David W. Thomas
Dr. Marc André Lécuyer
Guest Editors

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Keywords

  • T cell signaling
  • Ca signaling
  • TCR-activated signals
  • ER Ca release
  • ER Ca stores
  • store-operated Ca influx
  • ER Ca store depletion signals

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