| First Author | Mansour AA | Year | 2022 |
| Journal | Biomed Pharmacother | Volume | 151 |
| Pages | 113171 | PubMed ID | 35643073 |
| Mgi Jnum | J:349743 | Mgi Id | MGI:7311263 |
| Doi | 10.1016/j.biopha.2022.113171 | Citation | Mansour AA, et al. (2022) Galectin-9 supports primary T cell transendothelial migration in a glycan and integrin dependent manner. Biomed Pharmacother 151:113171 |
| abstractText | Adaptive immunity relies on the efficient recruitment of T cells from the blood into peripheral tissues. However, the current understanding of factor(s) coordinating these events is incomplete. Previous studies on galectin-9 (Gal-9), have proposed a functionally significant role for this lectin in mediating leukocyte adhesion and transmigration. However, very little is known about its function in T cell migration. Here, we have investigated the role of the Gal-9 on the migration behaviour of both human primary CD4(+) and CD8(+) T cells. Our data indicate that Gal-9 supports both CD4(+) and CD8(+) T cell adhesion and transmigration in a glycan dependent manner, inducing L-selectin shedding and upregulation of LFA-1 and CXCR4 expression. Additionally, when immobilized, Gal-9 promoted capture and firm adhesion of T cells under flow, in a glycan and integrin-dependent manner. Using an in vivo model, dorsal air pouch, we found that Gal-9 deficient mice display impaired leukocyte trafficking, with a reduction in pro-inflammatory cytokines/chemokines generated locally. Furthermore, we also demonstrate that Gal-9 inhibits the chemotactic function of CXCL12 through direct binding. In conclusion, our study characterises, for the first time, the capture, adhesion, and migration behaviour of CD4(+) and CD8(+) T cells to immobilised /endothelial presented Gal-9, under static and physiological flow conditions. We also demonstrate the differential binding characteristics of Gal-9 to T cell subtypes, which could be of potential therapeutic significance, particularly in the treatment of inflammatory-based diseases, given Gal-9 ability to promote apoptosis in pathogenic T cell subsets. |
