| First Author | Morrison VL | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 8 | Pages | 1428-36 |
| PubMed ID | 23823319 | Mgi Jnum | J:202261 |
| Mgi Id | MGI:5517751 | Doi | 10.1182/blood-2013-02-484998 |
| Citation | Morrison VL, et al. (2013) The beta2 integrin-kindlin-3 interaction is essential for T-cell homing but dispensable for T-cell activation in vivo. Blood 122(8):1428-36 |
| abstractText | Kindlin-3 is mutated in the rare genetic disorder, leukocyte adhesion deficiency type III, which is characterized by deficient integrin-mediated adhesion of leukocytes and platelets. However, the specific roles of kindlin-3-beta2-integrin interactions in T-cell adhesion and homing and immune responses in vivo remain unclear. Here, we show that the TTT motif in beta2 integrins controls kindlin-3 binding. Mutation of the kindlin-3 binding site in beta2 integrins caused a loss of firm adhesion of T cells under both static and shear flow conditions and a reduction of T-cell homing to lymph nodes in vivo. However, atomic force microscopy studies of integrin-ligand bonds revealed that initial ligand binding could still occur, and 2-dimensional T-cell migration was reduced but not abolished by the TTT/AAA mutation in the beta2 integrin. Importantly, dendritic cell-mediated T-cell activation in vivo was normal in TTT/AAA beta2 integrin knock-in mice. Our results reveal a selective role of the kindlin-3-integrin association for lymphocyte functions in vivo; the integrin-kindlin-3 interaction is particularly important in adhesion strengthening under shear flow, and for T-cell homing to lymph nodes, but dispensable for T cell activation which occurs in a shear-free environment. |
