First Author | Moretti FA | Year | 2018 |
Journal | Elife | Volume | 7 |
PubMed ID | 30187863 | Mgi Jnum | J:277471 |
Mgi Id | MGI:6331043 | Doi | 10.7554/eLife.35816 |
Citation | Moretti FA, et al. (2018) Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus. Elife 7:e35816 |
abstractText | The role of integrin-mediated adhesion during T cell progenitor homing to and differentiation within the thymus is ill-defined, mainly due to functional overlap. To circumvent compensation, we disrupted the hematopoietic integrin regulator kindlin-3 in mice and found a progressive thymus atrophy that is primarily caused by an impaired homing capacity of T cell progenitors to the vascularized thymus. Notably, the low shear flow conditions in the vascular system at midgestation allow kindlin-3-deficient fetal liver-derived T cell progenitors to extravasate via pharyngeal vessels and colonize the avascular thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceed without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell progenitor adhesion and signalling at low and indispensable at high shear forces. |