TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells.
Members of the T-cell immunoglobulin- and mucin-domain-containing molecule (TIM) family have roles in T-cell-mediated immune responses. TIM-1 and TIM-2 are predominantly expressed on T helper type 2 (Th2) cells, whereas TIM-3 is preferentially expressed on Th1 and Th17 cells. We found that TIM-1 and TIM-3, but neither TIM-2 nor TIM-4, were constitutively expressed on mouse peritoneal mast cells and bone marrow-derived cultured mast cells (BMCMCs). After IgE + Ag stimulation, TIM-1 expression was down-regulated on BMCMCs, whereas TIM-3 expression was up-regulated. We also found that recombinant mouse TIM-4 (rmTIM-4), which is a ligand for TIM-1, as well as an anti-TIM-3 polyclonal Ab, can promote interleukin-4 (IL-4), IL-6, and IL-13 production without enhancing degranulation in BMCMCs stimulated with IgE + Ag. Moreover, the anti-TIM-3 Ab, but neither anti-TIM-1 Ab nor rmTIM-4, suppressed mast-cell apoptosis. These observations suggest that TIM-1 and TIM-3 may be able to influence T-cell-mediated immune responses in part through effects on mast cells.
Nakae
Susumu
S
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
Iikura
Motoyasu
M
Suto
Hajime
H
Akiba
Hisaya
H
Umetsu
Dale T
DT
Dekruyff
Rosemarie H
RH
Saito
Hirohisa
H
Galli
Stephen J
SJ
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008407:Mast Cells / Q000378:metabolism*; D008565:Membrane Proteins / Q000145:classification / Q000378:metabolism*; D051379:Mice; D011991:Receptors, Virus / Q000145:classification / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; C442240:Havcr1 protein, mouse; C442241:Havcr2 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D011991:Receptors, Virus; C500399:TIM-4 protein, mouse