Article abstract
Nature Immunology 9, 415 - 423 (2008)
Published online: 9 March 2008 | doi:10.1038/ni1573
Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs
Hidenobu Kanda1, Rebecca Newton1,3, Russell Klein1,3, Yuka Morita1,3, Michael D Gunn2,3 & Steven D Rosen1
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.
- Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143, USA.
- Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143, USA.
- Present addresses: Office of the Gene Technology Regulator, Federal Government Department of Health, Canberra 2601, Australia (R.N.), Pulmonary and Critical Care Medicine Division, University of California Irvine, Orange, California 92868, USA (R.K.), Osaka University Faculty of Medicine, Osaka 565-0871, Japan (Y.M.) and Department of Medicine, Division of Cardiovascular Medicine, Duke University, Durham, North Carolina 27710, USA (M.D.G.).
Correspondence to: Steven D Rosen1 e-mail: steven.rosen@ucsf.edu
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