TIM-3 and its regulatory role in immune responses.
T cell immunoglobulin mucin-(TIM)-3 was first identified as a molecule specifically expressed on IFN-γ-secreting CD4(+) T helper 1 (Th1) and CD8(+) T cytotoxic (Tc1) cells in both mice and humans. TIM-3 acts as a negative regulator of Th1/Tc1 cell function by triggering cell death upon interaction with its ligand, galectin-9. This negative regulatory function of TIM-3 has now been expanded to include its involvement in establishing and/or maintaining a state of T cell dysfunction or "exhaustion" observed in chronic viral diseases. In addition, it is now appreciated that TIM-3 has other ligands and is expressed on other cell types, where it may function differently. Given that an increasing body of data support an important role for TIM-3 in both autoimmune and chronic inflammatory diseases in humans, deciphering the function of TIM-3 on different cell types during different immune conditions and how these can be regulated will be critical for harnessing the therapeutic potential of TIM-3 for the treatment of disease.
Zhu
Chen
C
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
Anderson
Ana C
AC
Kuchroo
Vijay K
VK
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002908:Chronic Disease; D037161:Galectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology*
D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008024:Ligands; D008565:Membrane Proteins