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Title

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

Authors
Moretti, Federico Andrea
Klapproth, Sarah
Ruppert, Raphael
Margraf, Andreas
Weber, Jasmin
Pick, Robert
Sperandio, Markus
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Published in eLife. 2018, vol. 7, p. 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.
Identifiers
PMID: 30187863
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Article (Published version) (9.3 MB) - public document Free access
Research group Groupe Christoph Scheiermann (995)
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MORETTI, Federico Andrea et al. Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus. In: eLife, 2018, vol. 7, p. e35816. https://archive-ouverte.unige.ch/unige:111546

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Deposited on : 2018-11-28

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