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Nat Immunol. 2008 Apr;9(4):415-23. doi: 10.1038/ni1573. Epub 2008 Mar 9.

Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs.

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1
Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143, USA.

Abstract

The extracellular lysophospholipase D autotaxin (ATX) and its product, lysophosphatidic acid, have diverse functions in development and cancer, but little is known about their functions in the immune system. Here we found that ATX had high expression in the high endothelial venules of lymphoid organs and was secreted. Chemokine-activated lymphocytes expressed receptors with enhanced affinity for ATX, which provides a mechanism for targeting the secreted ATX to lymphocytes undergoing recruitment. Lysophosphatidic acid induced chemokinesis in T cells. Intravenous injection of enzymatically inactive ATX attenuated the homing of T cells to lymphoid tissues, probably through competition with endogenous ATX and exertion of a dominant negative effect. Our results support the idea of a new and general step in the homing cascade in which the ectoenzyme ATX facilitates the entry of lymphocytes into lymphoid organs.

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PMID:
18327261
PMCID:
PMC2783613
DOI:
10.1038/ni1573
[Indexed for MEDLINE]
Free PMC Article

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