Extracellular galectin-3 preferentially through CD44 and PD-1 binds activated T cells and marks memory-phenotype T cell subsets
Abstract
BackgroundGalectin-3 (Gal-3) is a multifunctional β-galactoside-binding lectin implicated in immune regulation, yet its association with T cell phenotypes under physiological and inflammatory conditions remains incompletely defined.MethodsWe investigated Gal-3 expression and binding on murine and human T cells across developmental stages, tissues, sex, genetic background, circadian time, and inflammatory disease settings.ResultsIn mice, Gal-3-associated CD4+ and CD8+ T cells were dynamically regulated by age, anatomical location, strain, sex, and circadian rhythm. Gal-3+ T cells displayed increased activation markers, enhanced TCR-associated signaling molecules, elevated cytolytic mediators, increased proliferation, and greater apoptosis. Gal-3+ T cells were enriched within central and effector memory compartments and expressed higher levels of co-inhibitory receptors, including PD-1, with ImageStream analysis confirming Gal-3 co-expressed with PD-1. Recombinant Gal-3 preferentially bound activated, but not resting T cells, and associated with CD44 and CD3, suggesting activation-dependent acquisition of extracellular Gal-3. Re-analysis of human thymocyte and Long COVID single-cell RNA-seq datasets further supported an association between LGALS3 expression and activated/exhausted T cell states. Finally, intracellular staining indicated that T cells are unlikely to be a major source of Gal-3.ConclusionOur findings identify Gal-3 as a context-dependent marker and potential regulator of activated, antigen-experienced T cells, which promotes T cell apoptosis.
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BibTeX
@article{abouda2026extracellular,
title = {{Extracellular galectin-3 preferentially through CD44 and PD-1 binds activated T cells and marks memory-phenotype T cell subsets}},
author = {Amal Abouda and Emmanuel T. Alimo and Ako Azimi and AmirAli Bigleri and Amirhossein Rahmati and Shima Shahbaz and Shokrollah Elahi},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1940192},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940192},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extracellular galectin-3 preferentially through CD44 and PD-1 binds activated T cells and marks memory-phenotype T cell subsets
AU - Amal Abouda
AU - Emmanuel T. Alimo
AU - Ako Azimi
AU - AmirAli Bigleri
AU - Amirhossein Rahmati
AU - Shima Shahbaz
AU - Shokrollah Elahi
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1940192
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940192
AB - BackgroundGalectin-3 (Gal-3) is a multifunctional β-galactoside-binding lectin implicated in immune regulation, yet its association with T cell phenotypes under physiological and inflammatory conditions remains incompletely defined.MethodsWe investigated Gal-3 expression and binding on murine and human T cells across developmental stages, tissues, sex, genetic background, circadian time, and inflammatory disease settings.ResultsIn mice, Gal-3-associated CD4+ and CD8+ T cells were dynamically regulated by age, anatomical location, strain, sex, and circadian rhythm. Gal-3+ T cells displayed increased activation markers, enhanced TCR-associated signaling molecules, elevated cytolytic mediators, increased proliferation, and greater apoptosis. Gal-3+ T cells were enriched within central and effector memory compartments and expressed higher levels of co-inhibitory receptors, including PD-1, with ImageStream analysis confirming Gal-3 co-expressed with PD-1. Recombinant Gal-3 preferentially bound activated, but not resting T cells, and associated with CD44 and CD3, suggesting activation-dependent acquisition of extracellular Gal-3. Re-analysis of human thymocyte and Long COVID single-cell RNA-seq datasets further supported an association between LGALS3 expression and activated/exhausted T cell states. Finally, intracellular staining indicated that T cells are unlikely to be a major source of Gal-3.ConclusionOur findings identify Gal-3 as a context-dependent marker and potential regulator of activated, antigen-experienced T cells, which promotes T cell apoptosis.
SN - 1664-3224
ER -