Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking.
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.
Katagiri
Koko
K
Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Ohnishi
Noriko
N
Kabashima
Kenji
K
Iyoda
Tomonori
T
Takeda
Naoki
N
Shinkai
Yoichi
Y
Inaba
Kayo
K
Kinashi
Tatsuo
T
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
D016023:Integrins; D020827:rap1 GTP-Binding Proteins; C455831:Rassf5 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins