The autotaxin-LPA axis emerges as a novel regulator of lymphocyte homing and inflammation.
Lysophosphatidic acid (LPA) is a pleiotropic lipid molecule with potent effects on cell growth and motility. Major progress has been made in recent years in deciphering the mechanisms of LPA generation and how it acts on target cells. Most research has been conducted in other disciplines, but emerging data indicate that LPA has an important role to play in immunity. A key discovery was that autotaxin (ATX), an enzyme previously implicated in cancer cell motility, generates extracellular LPA from the precursor lysophosphatidylcholine. Steady-state ATX is expressed by only a few tissues, including high endothelial venules in lymph nodes, but inflammatory signals can upregulate ATX expression in different tissues. In this article, we review current thinking about the ATX/LPA axis in lymphocyte homing, as well as in models of allergic airway inflammation and asthma. New insights into the role of LPA in regulating immune responses should be forthcoming in the near future.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642.
Sara
S
Knowlden
Steve N
SN
Georas
D056704:Adaptive Immunity; D056151:Airway Remodeling / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007555:Isoxazoles / Q000494:pharmacology; D008221:Lymphoid Tissue / Q000276:immunology; D008246:Lysophospholipids / Q000032:analysis / Q000276:immunology*; D051379:Mice; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000276:immunology*; D011422:Propionates / Q000494:pharmacology; D011828:Radiation Chimera; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D014699:Venules / Q000276:immunology; D000099189:Lysophospholipase D
D000941:Antigens; D007555:Isoxazoles; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D011422:Propionates; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C477898:3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid; C032881:lysophosphatidic acid