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Valerie Dardalhon, Ana C Anderson, Jozsef Karman, Lionel Apetoh, Rucha Chandwaskar, David H Lee, Melanie Cornejo, Nozomu Nishi, Akira Yamauchi, Francisco J Quintana, Raymond A Sobel, Mitsuomi Hirashima, Vijay K Kuchroo, Tim-3/Galectin-9 Pathway: Regulation of Th1 Immunity through Promotion of CD11b+Ly-6G+ Myeloid Cells, The Journal of Immunology, Volume 185, Issue 3, August 2010, Pages 1383–1392, https://doi.org/10.4049/jimmunol.0903275
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Abstract
IFN-γ plays a central role in antitumor immunity. T cell Ig and mucin domain (Tim-3) is expressed on IFN-γ–producing Th1 cells; on interaction with its ligand, galectin-9, Th1 immunity is terminated. In this study, we show that transgenic overexpression of Tim-3 on T cells results in an increase in CD11b+Ly-6G+ cells and inhibition of immune responses. Molecular characterization of CD11b+Ly-6G+ cells reveals a phenotype consistent with granulocytic myeloid-derived suppressor cells. Accordingly, we find that modulation of the Tim-3/galectin-9 (Gal-9) pathway impacts on tumor growth. Similarly, overexpression of Tim-3 ligand, Gal-9, results in an increase in CD11b+Ly-6G+ cells and inhibition of immune responses. Loss of Tim-3 restores normal levels of CD11b+Ly-6G+ cells and normal immune responses in Gal-9 transgenic mice. Our data uncover a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses and identifies this pathway as a therapeutic target in diseases where myeloid-derived suppressor cells are disadvantageous.