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  The integrin coactivator Kindlin-3 is not required for lymphocyte diapedesis

Cohen, S. J., Gurevich, I., Feigelson, S. W., Petrovich, E., Moser, M., Shakhar, G., et al. (2013). The integrin coactivator Kindlin-3 is not required for lymphocyte diapedesis. BLOOD, 122(15), 2609-2617. doi:10.1182/blood-2013-04-495036.

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 Creators:
Cohen, Shmuel J.1, Author
Gurevich, Irina1, Author
Feigelson, Sara W.1, Author
Petrovich, Ekaterina1, Author
Moser, Markus2, Author           
Shakhar, Guy1, Author
Fassler, Reinhard2, Author           
Alon, Ronen1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: CD8(+) T-CELLS; HIGH ENDOTHELIAL VENULES; LEUKOCYTE ADHESION; DENDRITIC CELLS; INTERSTITIAL MIGRATION; AFFINITY REGULATION; DISTINCT ROLES; NODES; ACTIVATION; EFFECTOR
 Abstract: Kindlin-3 is an integrin-binding focal adhesion adaptor absent in patients with leukocyte and platelet adhesion deficiency syndrome and is critical for firm integrin-dependent leukocyte adhesion. The role of this adaptor in leukocyte diapedesis has never been investigated. In the present study, the functions of Kindlin-3 in this process were investigated in effector T lymphocytes trafficking to various lymphoid and nonlymphoid tissues. In vitro, Kindlin-3-deficient T cells displayed severely impaired lymphocyte function antigen-1-dependent lymphocyte adhesion but partially conserved very late antigen-4 adhesiveness. In vivo, the number of adoptively transferred Kindlin-3-deficient T effectors was dramatically elevated in the circulating pool compared with normal effectors, and the Kindlin-3 mutant effectors failed to enter inflamed skin lesions. The frequency of Kindlin-3-deficient T effectors arrested on vessel walls within inflamed skin-draining lymph nodes was also reduced. Strikingly, however, Kindlin-3-deficient effector T cells accumulated inside these vessels at significantly higher numbers than their wild-type lymphocyte counterparts and successfully extravasated into inflamed lymph nodes. Nevertheless, on entering these organs, the interstitial motility of these lymphocytes was impaired. This is the first in vivo demonstration that Kindlin-3-stabilized integrin adhesions, although essential for lymphocyte arrest on blood vessels and interstitial motility, are not obligatory for leukocyte diapedesis.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Issued
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: BLOOD
Source Genre: Journal
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Publ. Info: 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA : AMER SOC HEMATOLOGY
Pages: - Volume / Issue: 122 (15) Sequence Number: - Start / End Page: 2609 - 2617 Identifier: ISSN: 0006-4971