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

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.

• Authors: Federico Andrea Moretti, Sarah Klapproth, Raphael Ruppert, Andreas Margraf, Jasmin Weber, Robert Pick, Christoph Scheiermann, Markus Sperandio, Reinhard Fässler, Markus Moser
• Journal: eLife (Elife) Vol. 7 (09 06 2018) ISSN: 2050-084X [Electronic] England
• PMID: 30187863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018, Moretti et al.

Chemical References

• Cytoskeletal Proteins
• kindlin-3 protein, mouse

Topics

• Animals
• Animals, Newborn
• Atrophy
• Blood Flow Velocity
• Cell Adhesion
• Cell Proliferation
• Cytoskeletal Proteins (metabolism)
• Liver (cytology, embryology)
• Mice, Inbred C57BL
• Neovascularization, Physiologic
• Stem Cells (metabolism)
• T-Lymphocytes (cytology)
• Thymocytes (pathology)
• Thymus Gland (blood supply, pathology)