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

Moretti, Federico Andrea; Klapproth, Sarah; Ruppert, Raphael; Margraf, Andreas; Jasmin, Weber; Pick, Robert; Scheiermann, Christoph; Sperandio, Markus; Faessler, Reinhard and Moser, Markus (2018): Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus. In: eLife, Vol. 7, e35816

Abstract

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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2050-084X
• Language: English