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

Elife. 2018 Sep 6:7:e35816. doi: 10.7554/eLife.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.

Keywords: T cell homing; developmental biology; immunology; inflammation; integrin; kindlin-3; mouse; thymus development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Cytoskeletal Proteins
  • kindlin-3 protein, mouse