title: Regulation of T cell motility in vitro and in vivo by LPA and LPA2.
abstract: Lysophosphatidic acid (LPA) and the LPA-generating enzyme autotaxin (ATX) have been implicated in lymphocyte trafficking and the regulation of lymphocyte entry into lymph nodes. High local concentrations of LPA are thought to be present in lymph node high endothelial venules, suggesting a direct influence of LPA on cell migration. However, little is known about the mechanism of action of LPA, and more work is needed to define the expression and function of the six known G protein-coupled receptors (LPA 1-6) in T cells. We studied the effects of 18∶1 and 16∶0 LPA on naïve CD4+ T cell migration and show that LPA induces CD4+ T cell chemorepulsion in a Transwell system, and also improves the quality of non-directed migration on ICAM-1 and CCL21 coated plates. Using intravital two-photon microscopy, lpa2-/- CD4+ T cells display a striking defect in early migratory behavior at HEVs and in lymph nodes. However, later homeostatic recirculation and LPA-directed migration in vitro were unaffected by loss of lpa2. Taken together, these data highlight a previously unsuspected and non-redundant role for LPA2 in intranodal T cell motility, and suggest that specific functions of LPA may be manipulated by targeting T cell LPA receptors.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Knowlden
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Tara
authors.initials: T
authors.lastname: Capece
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Milan
authors.initials: M
authors.lastname: Popovic
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Chapman
authors.affiliation: Division of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Fariba
authors.initials: F
authors.lastname: Rezaee
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid