| First Author | Madireddi S | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 8 | Pages | 2721-2728 |
| PubMed ID | 28877989 | Mgi Jnum | J:251567 |
| Mgi Id | MGI:6103116 | Doi | 10.4049/jimmunol.1700575 |
| Citation | Madireddi S, et al. (2017) Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9. J Immunol 199(8):2721-2728 |
| abstractText | Stimulation of several TNF receptor family proteins has been shown to dampen inflammatory disease in murine models through augmenting the number and/or activity of regulatory T cells (Tregs). We recently found that one molecule, 4-1BB, used binding to Galectin-9 to exert its immunosuppressive effects and drive expansion of CD8(+)Foxp3(-) Tregs. We now show that ligation of another TNFR family molecule, DR3, which has previously been found to strongly expand CD4(+)Foxp3(+) Tregs and suppress inflammation, also requires Galectin-9. We found that the extracellular region of DR3 directly binds to Galectin-9, and that Galectin-9 associates with DR3 in Tregs. From studies in vitro with Galectin-9(-/-) CD4(+) T cells and Tregs, we found that stimulatory activity induced by ligating DR3 was in part dependent on Galectin-9. In vivo, in a model of experimental autoimmune encephalomyelitis, we show that an agonist of DR3 suppressed disease, correlating with expansion of CD4(+)Foxp3(+) Tregs, and this protective effect was lost in Galectin-9(-/-) mice. Similar results were seen in an allergic lung inflammation model. Thus, we demonstrate a novel function of Galectin-9 in facilitating activity of DR3 related to Treg-mediated suppression. |
