title: Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking.
abstract: Immunosurveillance requires the coordinated regulation of chemokines and adhesion molecules to guide immune cell migration. However, the critical molecule for governing the high trafficking capability of immune cells is not clear. Here we show that the effector molecule RAPL is indispensable in the integrin-mediated adhesion and migration of lymphocytes and dendritic cells. RAPL deficiency caused defective chemokine-triggered lymphocyte adhesion and migration to secondary lymphoid organs, resulting in atrophic lymphoid follicles and deficient marginal zone B cells, concomitant with increased immature B cells in the blood. Furthermore, splenic dendritic cells were diminished and defective in adhesion. After being activated with inflammatory stimuli, skin and splenic dendritic cells failed to migrate into either the draining lymph nodes or the white pulp of the spleen. Thus, RAPL is a crucial immune cell trafficking regulator essential for immunosurveillance.
authors.affiliation: Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Koko
authors.initials: K
authors.lastname: Katagiri
authors.forename: Noriko
authors.initials: N
authors.lastname: Ohnishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kinashi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002448:Cell Adhesion; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology*; D016023:Integrins / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D020827:rap1 GTP-Binding Proteins / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins
chemical_list: D016023:Integrins; D020827:rap1 GTP-Binding Proteins; C455831:Rassf5 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins