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Nat Immunol. 2004 Oct;5(10):1045-51. Epub 2004 Sep 7.

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

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

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.

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PMID:
15361866
DOI:
10.1038/ni1111
[Indexed for MEDLINE]
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