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Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus
- Source :
- eLife, Vol 7 (2018)
- Publication Year :
- 2018
- Publisher :
- eLife Sciences Publications Ltd, 2018.
-
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.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f0128f8be844499a97c496d39e30d830
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.35816