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The Tim-3 Ligand Galectin-9 Negatively Regulates T Helper Type 1 Immunity

C. Zhu, A. Anderson, Annette Schubart, H. Xiong, J. Imitola, Samia J Khoury, Xin Xiao Zheng, T. Strom, V. Kuchroo
Published 2005 · Biology, Medicine

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Tim-3 is a T helper type 1 (TH1)–specific cell surface molecule that seems to regulate TH1 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 TH1 cells remain unknown. Here we show that galectin-9 is the Tim-3 ligand. Galectin-9-induced intracellular calcium flux, aggregation and death of TH1 cells were Tim-3-dependent in vitro, and administration of galectin-9 in vivo resulted in selective loss of interferon-γ-producing cells and suppression of TH1 autoimmunity. These data suggest that the Tim-3–galectin-9 pathway may have evolved to ensure effective termination of effector TH1 cells.
This paper references
Ah, sweet mystery of death! Galectins and control of cell fate.
J. Hernandez (2002)
Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease
L. Monney (2002)
Apoptosis of alpha beta T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: its possible implications for recovery and acquired tolerance.
M. Pender (1992)
T cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human TH1 and TH2 cells and in NATURE IMMUNOLOGY VOLUME 6 NUMBER 12 DECEMBER
M Khademi (2005)
Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells.
H. Weiner (2001)
Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance
Catherine A. Sabatos (2003)
Tim-3 inhibits T helper type 1–mediated auto- and alloimmune responses and promotes immunological tolerance
A. Sánchez-Fueyo (2003)
Regulation of immunity to parasites by T cells and T cell-derived cytokines.
A. Sher (1992)
Human Galectin-2: Novel Inducer of T Cell Apoptosis with Distinct Profile of Caspase Activation1
A. Sturm (2004)
Requirement of Divalent Galactoside-binding Activity of Ecalectin/Galectin-9 for Eosinophil Chemoattraction*
N. Matsushita (2000)
Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes.
M. Lam (1994)
Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE).
I. Ferber (1996)
Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response?
G. Rabinovich (2002)
Interferon‐γ stimulates the expression of galectin‐9 in cultured human endothelial cells
T. Imaizumi (2002)
The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis.
Soo-Cheon Chae (2004)
Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family
Jennifer J. McIntire (2001)
TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.
T. Mosmann (1989)
Galectin-9 Induces Apoptosis Through the Calcium-Calpain-Caspase-1 Pathway1
Yumiko Kashio (2003)
Identification and Characterization of Galectin-9, a Novel β-Galactoside-binding Mammalian Lectin*
J. Wada (1997)
immune mechanisms and the generation of TH3-type TGFb-secreting regulatory cells
Weiner (2001)
Human Ecalectin, a Variant of Human Galectin-9, Is a Novel Eosinophil Chemoattractant Produced by T Lymphocytes*
R. Matsumoto (1998)
Interleukin-1β stimulates galectin-9 expression in human astrocytes
H. Yoshida (2001)
Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-Induced Arthritis via T Cell Apoptosis
G. Rabinovich (1999)
Lymphocyte responses and cytokines
W. Paul (1994)
Tolerance and autoimmunity.
T. Kamradt (2001)
Interferon-g stimulates the expression of galectin-9 in cultured human endothelial cells
T Imaizumi (2002)
novel inducer of T cell apoptosis with distinct profile of caspase activation
Sturm (2004)
Apoptosis of αβ T Lymphocytes in the Nervous System in Experimental Autoimmune Encephalomyelitis: Its Possible Implications for Recovery and Acquired Tolerance
M. Pender (1992)
T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis1
M. Khademi (2004)
amplifiers, silencers or tuners of the inflammatory response? Trends Immunol
Rabinovich (2002)
Selective eosinophil adhesion to fibroblast via IFN-γ-induced galectin-9
朝倉 浩文 (2002)
Soluble lactose-binding lectin from rat intestine with two different carbohydrate-binding domains in the same peptide chain.
Y. Oda (1993)
Functional diversity of T lymphocytes due to secretion of different cytokine patterns
N. Street (1991)
Lymphokine production by human T cells in disease states.
S. Romagnani (1994)
Dual Signaling of the Fas Receptor: Initiation of Both Apoptotic and Necrotic Cell Death Pathways
D. Vercammen (1998)
Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin.
J. Wada (1997)
Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis
A. Salama (2003)
initiation of both apoptotic and necrotic cell death pathways
Vercammen (1998)
Functional diversity of helper T lymphocytes
A. Abbas (1996)

This paper is referenced by
DNA demethylation of the TIM-3 promoter is critical for its stable expression on T cells
F-C Chou (2016)
Effects of Single Genetic Damage in Carbohydrate‐Recognizing Proteins in Mouse Serum N‐Glycan Profile Revealed by Simple Glycotyping Analysis
Maho Amano (2012)
Galectin‐9: a suppressor of food allergy?
Erna Sziksz (2012)
Coupling pathogen recognition to innate immunity through glycan-dependent mechanisms.
R. Davicino (2011)
T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment.
J. Crespo (2013)
Protective HIV-specific CD8+ T cells evade Treg cell suppression
S. Elahi (2011)
Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti–Tim-3 antibody in vivo
J. Kearley (2007)
TIM family proteins and autoimmunity
L. Kane (2007)
Unique sequence and expression profiles of rat galectins-5 and -9 as a result of species-specific gene divergence.
M. Lensch (2006)
X-ray Structures of Human Galectin-9 C-terminal Domain in Complexes with a Biantennary Oligosaccharide and Sialyllactose*
H. Yoshida (2010)
Expression of the Tim3‐galectin‐9 axis is altered in drug‐induced maculopapular exanthema
R. Fernández-Santamaría (2019)
How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair
P. Gál (2017)
Melanoma: oncogenic drivers and the immune system.
N. Karachaliou (2015)
Dysregulation of FTX/miR‐545 signaling pathway downregulates Tim‐3 and is responsible for the abnormal activation of macrophage in cirrhosis
X. Liu (2018)
Human Cytomegalovirus Upregulates Expression of the Lectin Galectin 9 via Induction of Beta Interferon
B. McSharry (2014)
High resolution X-ray and NMR structural study of human T-cell immunoglobulin and mucin domain containing protein-3
A. Gandhi (2018)
Tim-3 signaling blockade with α-lactose induces compensatory TIGIT expression in Plasmodium berghei ANKA-infected mice
Yi-wei Zhang (2019)
Induction, control, and plasticity of Treg cells: The immune regulatory network revised?
V. Barnaba (2013)
TIM-3 Regulates Distinct Functions in Macrophages
Ranferi Ocaña-Guzman (2016)
Synthesis and screening of a small glycomimetic library for inhibitory activity on medically relevant galactoside-specific lectins in assays of increasing biorelevance
S. André (2010)
Microenvironmental Determinants of Pancreatic Cancer.
Elisabeth Hessmann (2020)
Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) regulate CD4+ T cells to induce Type 2 helper T cell (Th2) bias at the maternal-fetal interface.
Songcun Wang (2016)
Tim-3/Gal-9 and B7-H3 act as negative regulators of graft versus host disease
Rachelle G. Veenstra (2013)
The immune microenvironment of sarcomas : a comprehensive evaluation of infiltrating immune cells and checkpoint biomarkers in musculoskeletal tumors
Amanda R. Dancsok (2019)
Modulating the function of T cell immunoglobulin mucin cell surface proteins for therapeutic immunoregulation
Involvement of Galectin-9 in Guinea Pig Allergic Airway Inflammation
H. Yamamoto (2007)
Regulatory mechanisms of nucleic acid-mediated innate immune responses in the tumor microenvironment
M. Jinushi (2012)
Increased expression of Tim-3 and its ligand Galectin-9 in rat allografts during acute rejection episodes.
Xin-wei Qiao (2014)
TIM-3 and Its Immunoregulatory Role in HIV Infection
A. Rahman (2013)
Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis.
Zhengping Wei (2018)
Next generation immune-checkpoints for cancer therapy.
Chiara Donini (2018)
Different angioregulatory activity of monovalent galectin-9 isoforms
Ed Aanhane (2018)
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