The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity.
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.
Zhu
Chen
C
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Anderson
Ana C
AC
Schubart
Anna
A
Xiong
Huabao
H
Imitola
Jaime
J
Khoury
Samia J
SJ
Zheng
Xin Xiao
XX
Strom
Terry B
TB
Kuchroo
Vijay K
VK
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D037161:Galectins / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D037161:Galectins; D006023:Glycoproteins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008024:Ligands; D011991:Receptors, Virus; D007371:Interferon-gamma