title: AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation.
abstract: The mechanisms driving T cell homing to lymph nodes and migration to tissue are well described but little is known about factors that affect T cell egress from tissues. Here, we generate mice with a T cell-specific deletion of the scaffold protein A kinase anchoring protein 9 (AKAP9) and use models of inflammatory disease to demonstrate that AKAP9 is dispensable for T cell priming and migration into tissues and lymph nodes, but is required for T cell retention in tissues. AKAP9 deficiency results in increased T cell egress to draining lymph nodes, which is associated with impaired T cell re-activation in tissues and protection from organ damage. AKAP9-deficient T cells exhibit reduced microtubule-dependent recycling of TCRs back to the cell surface and this affects antigen-dependent activation, primarily by non-classical antigen-presenting cells. Thus, AKAP9-dependent TCR trafficking drives efficient T cell re-activation and extends their retention at sites of inflammation with implications for disease pathogenesis.
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Herter
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Grabie
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cullere
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Azcutia
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Florencia
authors.initials: F
authors.lastname: Rosetti
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Bennett
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Grit S
authors.initials: GS
authors.lastname: Herter-Sprie
authors.affiliation: Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Wassim
authors.initials: W
authors.lastname: Elyaman
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Francis W
authors.initials: FW
authors.lastname: Luscinskas
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Lichtman
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Mayadas
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D011992:Endosomes; D055786:Gene Knockout Techniques; D050533:Glomerular Basement Membrane / Q000276:immunology; D066298:In Vitro Techniques; D007249:Inflammation; D007668:Kidney / Q000098:blood supply / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000276:immunology; D009393:Nephritis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell; D015427:Reperfusion Injury / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology
chemical_list: D054758:A Kinase Anchor Proteins; C464931:Akap9 protein, mouse; D008869:Microtubule-Associated Proteins; D011948:Receptors, Antigen, T-Cell