The TIM gene family regulates autoimmune and allergic diseases.
The recently identified TIM gene family encodes cell-surface receptors that are involved in the regulation of Th1- and Th2-cell-mediated immunity. Tim-3 protein is specifically expressed on Th1 cells and negatively regulates Th1 responses, whereas Tim-2 is preferentially expressed in Th2 cells. Tim-1, previously identified as the hepatitis A virus receptor, co-stimulates T-cell expansion and cytokine production. Tim-4, which is preferentially expressed on mature dendritic cells, is the ligand for Tim-1. In mouse models of asthma and multiple sclerosis, affecting the function of Tim molecules altered disease phenotype. Because TIM molecules are differentially expressed on effector Th1 and Th2 cells, further understanding of the mechanisms by which they regulate Th1- and Th2-effector functions will probably provide opportunities for the therapeutic modulation of immune-mediated diseases.
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Ave. Louis Pasteur, HIM/Room 780, Boston, MA 02115, USA.
Jennifer Hartt
JH
Meyers
Catherine A
CA
Sabatos
Sumone
S
Chakravarti
Vijay K
VK
Kuchroo
D000818:Animals; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007154:Immune System Diseases / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D011991:Receptors, Virus / Q000235:genetics* / Q000276:immunology; D012130:Respiratory Hypersensitivity; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; C491143:HAVCR1 protein, human; C448908:HAVCR2 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C500399:TIM-4 protein, mouse; C442242:Timd2 protein, mouse