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Article
Nature Immunology  5, 1045 - 1051 (2004)
Published online: 7 September 2004; | doi:10.1038/ni1111

Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking

Koko Katagiri1, Noriko Ohnishi1, Kenji Kabashima2, Tomonori Iyoda3, Naoki Takeda4, Yoichi Shinkai5, Kayo Inaba3 & Tatsuo Kinashi1

1  Department of Molecular Immunology and Allergy, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

2  Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

3  Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.

4  Center for Animal Resources and Development, Kumamoto University, Kumamoto 860-0811, Japan.

5  Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan.

Correspondence should be addressed to Tatsuo Kinashi tkinashi@mfour.med.kyoto-u.ac.jp
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.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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