Calcium signalling in lymphocyte activation and disease
Abstract
Calcium signals in cells of the immune system participate in the regulation of cell differentiation, gene transcription and effector functions. An increase in intracellular levels of calcium ions (Ca2+) results from the engagement of immunoreceptors, such as the T-cell receptor, B-cell receptor and Fc receptors, as well as chemokine and co-stimulatory receptors. The major pathway that induces an increase in intracellular Ca2+ levels in lymphocytes is through store-operated calcium entry (SOCE) and calcium-release-activated calcium (CRAC) channels. This Review focuses on the role of Ca2+ signals in lymphocyte functions, the signalling pathways leading to Ca2+ influx, the function of the recently discovered regulators of Ca2+ influx (STIM and ORAI), and the relationship between Ca2+ signals and diseases of the immune system.
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NFAT plays a critical role in T cell differentiation and response.
“NFAT is known to play a critical role in T cell differentiation and response (30, 59).”
From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [59]
In the canonical NFAT pathway, Ca2+/Calcineurin mediates nuclear translocation of NFAT through the dephosphorylation of multiple serine residues in the N-terminus region, including the nuclear localization signal.
“In the canonical NFAT pathway, Ca2+/Calcineurin mediates nuclear translocation of NFAT through the dephosphorylation of multiple serine residues in the N-terminus region, including the nuclear localization signal (34, 59, 60).”
From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [59]
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“Moreover, it will be important to determine the functional roles of the recently identified ORAI1 and STIM proteins in CD28SA-induced transmembrane Caflux [40].”
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- Authors
- Feske, S.
- Affiliations
- NYU Langone Health (US)
- Corresponding author
- Feske, Stefan
- ORCID
- Feske, Stefan
- Venue
- Nature Reviews Immunology
- Published
- 2007-08-17
- Volume
- 7
- Issue
- 9
- Pages
- 690-702
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2041748354
- Cited by
- 1,043
- References
- 1
- Citations by year
- 2026: 33 · 2025: 34 · 2024: 38 · 2023: 47 · 2022: 44 · 2021: 52 · 2020: 53 · 2019: 49 · 2018: 61 · 2017: 52 · 2016: 62 · 2015: 64 · 2014: 44 · 2013: 68 · 2012: 63
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI066128, R01AI066128)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- calcium signaling, lymphocyte activation, store-operated calcium entry, STIM, Orai, CRAC channels, calcium influx, T cell receptor, B cell receptor, Fc receptors, costimulatory receptors, chemokine receptors, immune disorders, intracellular calcium
- MeSH terms
- Stromal Interaction Molecule 1, ORAI1 Protein, Animals, Calcium, Humans, Lymphocyte Activation, Lymphocytes, Membrane Proteins, Neoplasm Proteins, Calcium Channels, Autoimmunity, Severe Combined Immunodeficiency, Calcium Signaling
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