| First Author | Ju Y | Year | 2014 |
| Journal | Mol Immunol | Volume | 58 |
| Issue | 1 | Pages | 85-91 |
| PubMed ID | 24333756 | Mgi Jnum | J:206298 |
| Mgi Id | MGI:5550000 | Doi | 10.1016/j.molimm.2013.11.001 |
| Citation | Ju Y, et al. (2014) The Tim-3/galectin-9 pathway involves in the homeostasis of hepatic Tregs in a mouse model of concanavalin A-induced hepatitis. Mol Immunol 58(1):85-91 |
| abstractText | T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is a negative regulator of interferon (IFN)-gamma-secreting CD4(+) Th1 cells and plays a key role in autoimmune diseases. Here, we report that galectin-9 expression was increased in hepatic CD4(+)CD25(+) T cells in a mouse model of concanavalin A (Con A)-induced hepatitis. Moreover, Tim-3 showed increased levels in CD4(+)CD25(+) Foxp3(+) regulatory T cells (Tregs). Further analyses showed that blocking the Tim-3/galectin-9 pathway resulted in the suppression of Tregs in vitro, thereby significantly increasing interferon (IFN)-gamma production from hepatic Teffs. Moreover, blockade of Tim-3 in vivo with an anti-Tim-3 antibody exacerbated the acute hepatitis, possibly by increased IFN-gamma production. Furthermore, we found that in vitro activation of CD4(+)CD25(-) T cells with the T cell receptor (TCR) plus interleukin 2 (IL-2) up-regulated Tim-3 expression. And the induced Tim-3 interacted with galectin-9 to induce CD4(+) T cell apoptosis which could be partly reversed by blocking Tim-3 signaling. Our results suggested that the Tim-3/galectin-9 pathway plays a critical role in the homeostasis of hepatic Tregs through the elimination induction in Teffs and the inhibition of IFN-gamma release, which contributes to the pathogenesis of liver damage and constitutes at least part of the mechanism underlying the induction of hepatitis by Con A. |
