Submitted November 20, 2006
Accepted June 21, 2007
TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells
Susumu Nakae, Motoyasu Iikura, Hajime Suto, Hisaya Akiba, Dale T Umetsu, Rosemarie H DeKruyff, Hirohisa Saito, and Stephen J Galli*
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
Atopy Research Center, Juntendo University, Tokyo, Japan
Department of Immunology, Juntendo University, Tokyo, Japan
Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, MA, United States
Department of Allergy & Immunology, National Research Institute for Child Health & Development, Tokyo, Japan
* Corresponding author; email: sgalli{at}stanford.edu.
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 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 downregulated on BMCMCs, whereas TIM-3 expression was upregulated. 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 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.
