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

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