Cited by 2,057Galectins and Cancer BiologyT-cell and B-cell ImmunologyImmune Response and Inflammation

The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity

Zhu, Chen, Anderson, Ana C, Schubart, Anna, Xiong, Huabao, Imitola, Jaime, Khoury, Samia J, Zheng, Xin Xiao, Strom, Terry B +1 more·2005·Nature Immunology

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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Crossref · 10.1038/ni1271

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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
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
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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