| First Author | Li Y | Year | 2011 |
| Journal | Mol Immunol | Volume | 48 |
| Issue | 4 | Pages | 670-7 |
| PubMed ID | 21146220 | Mgi Jnum | J:167038 |
| Mgi Id | MGI:4867091 | Doi | 10.1016/j.molimm.2010.11.011 |
| Citation | Li Y, et al. (2011) The N- and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity. Mol Immunol 48(4):670-7 |
| abstractText | By binding to T cell Ig mucin-3 (Tim-3) expressed on different cells, galectin-9 (Gal-9) mediates two important functions, triggering T cell death and activating innate immune cells. The mechanisms by which ligation of the same molecule on different cell types mediates different effects are largely unclear. Gal-9 contains two carbohydrate recognition domains (CRD) in the N- and C-terminal regions (Gal-9-N and Gal-9-C). The N and C terminals of Gal-9 have been shown to have different activities in promoting T cell death. However, whether the differences between two domains account for its dual functions remains to be elucidated. Here we hypothesized that the different functions of Gal-9 in innate immunity and adaptive immunity are mediated by different domains. To test this, we created recombinant Gal-9 (Gal-9-NC) and homodimers containing either the NCRD (Gal-9-N) or the CCRD (Gal-9-C). All these Gal-9 constructs can activate dendritic cells (DCs) and induce T cell death. However, the Gal-9-C was much more potent than the Gal-9-N in inducing T cell death, while the Gal-9-N was much more effective in activating DCs by inducing much higher TNF-alpha and IL-6 production, greater phosphorylation of p38 and AKT. In both DC and T cells, Gal-9-N but not Gal-9-C stimulation resulted in markedly ikappaBalpha degradation. Finally, computer analyses suggested different patterns and affinities for the binding of the Gal-9-N and Gal-9-C to their receptor, Tim-3. Our data suggest that the N- and C-terminal CRDs of Gal-9 contribute differently to its ability to induce T cell death and to activate DCs. Further investigations on the underlying mechanisms will provide new insights into the biochemical basis for the multiple activities of Gal-9. |
