title: The integrin coactivator Kindlin-3 is not required for lymphocyte diapedesis.
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.
authors: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; and.
authors: Shmuel J
authors: SJ
authors: Cohen
authors: Irina
authors: I
authors: Gurevich
authors: Sara W
authors: SW
authors: Feigelson
authors: Ekaterina
authors: E
authors: Petrovich
authors: Markus
authors: M
authors: Moser
authors: Guy
authors: G
authors: Shakhar
authors: Reinhard
authors: R
authors: Fassler
authors: Ronen
authors: R
authors: Alon
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000276:immunology*; D003872:Dermatitis / Q000276:immunology / Q000473:pathology; D006801:Humans; D039041:Integrin alpha4beta1 / Q000276:immunology; D008199:Lymphadenitis / Q000276:immunology / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology* / Q000473:pathology
chemical_list: D003598:Cytoskeletal Proteins; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; C527818:kindlin-3 protein, mouse