The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity
Abstract
Tim-3 is a T helper type 1 (T(H)1)-specific cell surface molecule that seems to regulate T(H)1 responses and the induction of peripheral tolerance. However, the identity of the Tim-3 ligand and the mechanism by which this ligand inhibits the function of effector T(H)1 cells remain unknown. Here we show that galectin-9 is the Tim-3 ligand. Galectin-9-induced intracellular calcium flux, aggregation and death of T(H)1 cells were Tim-3-dependent in vitro, and administration of galectin-9 in vivo resulted in selective loss of interferon-gamma-producing cells and suppression of T(H)1 autoimmunity. These data suggest that the Tim-3-galectin-9 pathway may have evolved to ensure effective termination of effector T(H)1 cells.
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Galectin-9 is the ligand for Tim-3.
“Galectin-9 is the Tim-3 ligand.”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [65]
Galectin-9 induces intracellular calcium flux, aggregation, and death of Th1 cells in a Tim-3-dependent manner.
“Galectin-9 induces intracellular calcium flux, aggregation and death of Th1 cells in Tim-3-dependent manner [65].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [65]
The engagement of TIM-3 with its ligand galectin-9 led to Th1 cell death by triggering intracellular calcium flux.
“The engagement of TIM-3 with its ligand galectin-9 led to Th1 cell death by triggering intracellular calcium flux [156].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [156]
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- Authors
- Zhu, C., Anderson, A. C., Schubart, A., Xiong, H., Imitola, J., Khoury, S. J., Zheng, X. X., Strom, T. B., & Kuchroo, V. K.
- Affiliations
- Brigham and Women's Hospital (US)
- New York University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Kuchroo, Vijay K
- ORCID
- Venue
- Nature Immunology
- Published
- 2005-11-13
- Volume
- 6
- Issue
- 12
- Pages
- 1245-1252
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2070631889
- Cited by
- 2,057
- References
- 33
- Citations by year
- 2026: 78 · 2025: 125 · 2024: 146 · 2023: 134 · 2022: 144 · 2021: 154 · 2020: 149 · 2019: 126 · 2018: 125 · 2017: 118 · 2016: 109 · 2015: 106 · 2014: 91 · 2013: 92 · 2012: 85
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TIM-3, galectin-9, T helper type 1 cells, T cell tolerance, interferon-gamma, autoimmunity, T cell death, calcium flux, immune checkpoint
- MeSH terms
- Hepatitis A Virus Cellular Receptor 2, Amino Acid Sequence, Animals, Cells, Cultured, Female, Glycoproteins, Immunity, Cellular, Interferon-gamma, Ligands, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Protein Binding, Receptors, Virus, Down-Regulation, Th1 Cells, Galectins, Mice
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