Galectin-1 Sensitizes Resting Human T Lymphocytes to Fas (CD95)-mediated Cell Death via Mitochondrial Hyperpolarization, Budding, and Fission
Open accessAbstract
Galectins have emerged as a novel family of immunoregulatory proteins implicated in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key role in tumor-immune escape by killing antitumor effector T cells. Here we found that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell death. Furthermore, this protein triggers an apoptotic program involving an increase of mitochondrial membrane potential and participation of the ceramide pathway. In addition, Gal-1 induces mitochondrial coalescence, budding, and fission accompanied by an increase and/or redistribution of fission-associated molecules h-Fis and DRP-1. Importantly, these changes are detected in both resting and activated human T cells, suggesting that Gal-1-induced cell death might become an excellent model to analyze the morphogenetic changes of mitochondria during the execution of cell death. This is the first association among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway, providing a rational basis for the immunoregulatory properties of Gal-1 in experimental models of chronic inflammation and cancer.
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Glycosylation state of some death receptors (e.g., FAS) impacts sensitivity of T lymphocytes to extrinsic apoptosis, influencing termination of inflammatory responses.
“Of note, the glycosylation state of some death receptors (e.g., FAS) has been shown to impact on the sensitivity of T lymphocytes to extrinsic apoptosis, hence influencing the termination of inflammatory responses [288–290].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [290]
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- Authors
- Matarrese, P., Tinari, A., Mormone, E., Bianco, G. A., Toscano, M. A., Ascione, B., Rabinovich, G. A., & Malorni, W.
- Affiliations
- Istituto Superiore di Sanità (IT)
- Universidad de Buenos Aires (AR)
- Corresponding author
- Malorni, Walter
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 280
- Issue
- 8
- Pages
- 6969-6985
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1978720466
- Cited by
- 182
- References
- 53
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 9 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 8 · 2012: 9
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Greater South Information System
- Funders
- Fundación Antorchas
- Wellcome Trust
- Fundación Sales
- Universidad de Buenos Aires
- Secretaría de Ciencia y Técnica, Universidad de Buenos Aires
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- galectin-1, T cells, mitochondrial hyperpolarization, mitochondrial fission, ceramide pathway, Drp1, caspase-8, immune regulation, tumor immune evasion, chronic inflammation
- MeSH terms
- Cells, Cultured, Humans, Intracellular Membranes, Membrane Potentials, Membrane Proteins, Mitochondria, T-Lymphocytes, Apoptosis, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, fas Receptor, Tumor Escape, Caspases, Mitochondrial Proteins, Galectin 1, Apoptosis Regulatory Proteins, Caspase 8, Death-Associated Protein Kinases
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