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

Moretti, F. A., Klapproth, S., Ruppert, R., Margraf, A., Jasmin, W., Pick, R., et al. (2018). Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus. eLife, 7: e35816. doi:10.7554/eLife.35816.

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 Creators:
Moretti, Federico Andrea1, Author              
Klapproth, Sarah1, Author              
Ruppert, Raphael1, Author              
Margraf, Andreas2, Author
Jasmin, Weber2, Author
Pick, Robert2, Author
Scheiermann, Christoph2, Author
Sperandio, Markus2, Author
Fässler, Reinhard1, Author              
Moser, Markus1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: INTEGRIN COACTIVATOR KINDLIN-3; HEMATOPOIETIC STEM-CELLS; FETAL LIVER-CELLS; LEUKOCYTE ADHESION; IN-VIVO; BONE-MARROW; MICE; ACTIVATION; PRECURSORS; MIGRATIONLife Sciences & Biomedicine - Other Topics;
 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.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published online
 Pages: 28
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000443931900001
DOI: 10.7554/eLife.35816
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Title: eLife
Source Genre: Journal
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Publ. Info: Cambridge : eLife Sciences Publications
Pages: - Volume / Issue: 7 Sequence Number: e35816 Start / End Page: - Identifier: ISSN: 2050-084X
CoNE: https://pure.mpg.de/cone/journals/resource/2050-084X