Cargando…

Involvement of mTOR in CXCL12 Mediated T Cell Signaling and Migration

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 rap...

Descripción completa

Detalles Bibliográficos
Autores principales: Munk, Rachel, Ghosh, Paritosh, Ghosh, Manik C., Saito, Takeshi, Xu, Mai, Carter, Arnell, Indig, Fred, Taub, Dennis D., Longo, Dan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171460/
https://www.ncbi.nlm.nih.gov/pubmed/21931802
http://dx.doi.org/10.1371/journal.pone.0024667
Descripción
Sumario: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. METHODOLOGY/PRINCIPAL FINDINGS: 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.