Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells.
CD4+ T helper 1 (TH1) cells are important mediators of inflammation and are regulated by numerous pathways, including the negative immune receptor Tim-3. We found that Tim-3 is constitutively expressed on cells of the innate immune system in both mice and humans, and that it can synergize with Toll-like receptors. Moreover, an antibody agonist of Tim-3 acted as an adjuvant during induced immune responses, and Tim-3 ligation induced distinct signaling events in T cells and dendritic cells; the latter finding could explain the apparent divergent functions of Tim-3 in these cell types. Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions.
Anderson
Ana C
AC
Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Anderson
David E
DE
Bregoli
Lisa
L
Hastings
William D
WD
Kassam
Nasim
N
Lei
Charles
C
Chandwaskar
Rucha
R
Karman
Jozsef
J
Su
Ee W
EW
Hirashima
Mitsuomi
M
Bruce
Jeffrey N
JN
Kane
Lawrence P
LP
Kuchroo
Vijay K
VK
Hafler
David A
DA
D000818:Animals; D001253:Astrocytes / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D016543:Central Nervous System Neoplasms / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D037161:Galectins / Q000276:immunology; D005909:Glioblastoma / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D017628:Microglia / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology; D051381:Rats; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D011991:Receptors, Virus / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D051193:Toll-Like Receptors
D039481:CD11b Antigen; D037161:Galectins; C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; C509295:ITGAM protein, human; D018836:Inflammation Mediators; C105032:LGALS9 protein, human; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D051193:Toll-Like Receptors