| First Author | Golden-Mason L | Year | 2013 |
| Journal | J Virol | Volume | 87 |
| Issue | 9 | Pages | 4835-45 |
| PubMed ID | 23408620 | Mgi Jnum | J:197208 |
| Mgi Id | MGI:5491117 | Doi | 10.1128/JVI.01085-12 |
| Citation | Golden-Mason L, et al. (2013) Galectin-9 functionally impairs natural killer cells in humans and mice. J Virol 87(9):4835-45 |
| abstractText | Galectin-9 is a pleiotropic immune modulator affecting numerous cell types of innate and adaptive immunity. Patients with chronic infection with either hepatitis C virus (HCV) or HIV have elevated circulating levels. Limited data exist on the regulation of natural killer (NK) cell function through interaction with galectin-9. We found that galectin-9 ligation downregulates multiple immune-activating genes, including eight involved in the NK cell-mediated cytotoxicity pathway, impairs lymphokine-activated killing, and decreases the proportion of gamma interferon (IFN-gamma)-producing NK cells that had been stimulated with interleukin-12 (IL-12)/IL-15. We demonstrate that the transcriptional and functional changes induced by galectin-9 are independent of Tim-3. Consistent with these results for humans, we find that the genetic absence of galectin-9 in mice is associated with greater IFN-gamma production by NK cells and enhanced degranulation. We also show that in the setting of a short-term (4-day) murine cytomegalovirus infection, terminally differentiated NKs accumulate in the livers of galectin-9 knockout mice, and that hepatic NKs spontaneously produce significantly more IFN-gamma in this setting. Taken together, our results indicate that galectin-9 engagement impairs the function of NK cells, including cytotoxicity and cytokine production. |
