| First Author | Mohammed RN | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 5487 |
| PubMed ID | 30940840 | Mgi Jnum | J:279868 |
| Mgi Id | MGI:6357503 | Doi | 10.1038/s41598-019-41811-z |
| Citation | Mohammed RN, et al. (2019) ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells. Sci Rep 9(1):5487 |
| abstractText | L-selectin on T-cells is best known as an adhesion molecule that supports recruitment of blood-borne naive and central memory cells into lymph nodes. Proteolytic shedding of the ectodomain is thought to redirect activated T-cells from lymph nodes to sites of infection. However, we have shown that activated T-cells re-express L-selectin before lymph node egress and use L-selectin to locate to virus-infected tissues. Therefore, we considered other roles for L-selectin proteolysis during T cell activation. In this study, we used T cells expressing cleavable or non-cleavable L-selectin and determined the impact of L-selectin proteolysis on T cell activation in virus-infected mice. We confirm an essential and non-redundant role for ADAM17 in TCR-induced proteolysis of L-selectin in mouse and human T cells and show that L-selectin cleavage does not regulate T cell activation measured by CD69 or TCR internalisation. Following virus infection of mice, L-selectin proteolysis promoted early clonal expansion of cytotoxic T cells resulting in an 8-fold increase over T cells unable to cleave L-selectin. T cells unable to cleave L-selectin showed delayed proliferation in vitro which correlated with lower CD25 expression. Based on these results, we propose that ADAM17-dependent proteolysis of L-selectin should be considered a regulator of T-cell activation at sites of immune activity. |
