Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus

• Main Authors: Federico Andrea Moretti, Sarah Klapproth, Raphael Ruppert, Andreas Margraf, Jasmin Weber, Robert Pick, Christoph Scheiermann, Markus Sperandio, Reinhard Fässler, Markus Moser
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2018-09-01
• Series: eLife
• Subjects: kindlin-3; integrin; T cell homing; thymus development
• Online Access: https://elifesciences.org/articles/35816

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.