title: Involvement of mTOR in CXCL12 mediated T cell signaling and migration.
abstract: BACKGROUND
  CXCL12 is a pleiotropic chemokine involved in multiple different processes such as immune regulation, inflammatory responses, and cancer development. CXCL12 is also a potent chemokine involved in chemoattraction of T cells to the site of infection or inflammation. Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that modulates different cellular processes, such as metabolism, nutrient sensing, protein translation, and cell growth. The role of mTOR in CXCL12-mediated resting T cell migration has yet to be elucidated.
  
  
  RESULTS
  Rapamycin, an inhibitor of mTOR, significantly inhibits CXCL12 mediated migration of both primary human resting T cells and human T cell leukemia cell line CEM. p70(S6K1), an effector molecule of mTOR signaling pathway, was knocked down by shRNA in CEM cells using a lentiviral gene transfer system. Using p70(S6K1) knock down cells, we demonstrate the role of mTOR signaling in T cell migration both in vitro and in vivo.
  
  
  CONCLUSIONS
  Our data demonstrate a new role for mTOR in CXCL12-induced T cell migration, and enrich the current knowledge regarding the clinical use of rapamycin.
authors.affiliation: Lymphocyte Cell Biology Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Munk
authors.forename: Paritosh
authors.initials: P
authors.lastname: Ghosh
authors.forename: Manik C
authors.initials: MC
authors.lastname: Ghosh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Mai
authors.initials: M
authors.lastname: Xu
authors.forename: Arnell
authors.initials: A
authors.lastname: Carter
authors.forename: Fred
authors.initials: F
authors.lastname: Indig
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus