biostudies-literatureFujiwara MNational Multiple Sclerosis SocietyNIAID NIH HHSNational Institute of HealthCSR NIH HHS103-13https://www.ebi.ac.uk/biostudies/studies/S-EPMC4420730biostudies-literatureUnknown158(1)The variable response to therapy in multiple sclerosis (MS) suggests a need for personalized approaches based on individual genetic differences. GWAS have linked CBLB gene polymorphisms with MS and recent evidence demonstrated that these polymorphisms can be associated with abnormalities in T cell function and response to interferon-β therapy. Cbl-b is an E3 ubiquitin ligase that regulates T cell activation and Cbl-b-deficient (Cbl-b(-/-)) mice show T cell abnormalities described in MS patients. We now show that Cbl-b(-/-) T cells demonstrate significant lymph node trafficking abnormalities. We thus asked whether the MS-approved drug, FTY720, postulated to trap T cells in lymphoid tissues, is less effective in the context of Cbl-b dysfunction. We now report that FTY720 significantly inhibiClinical immunology (Orlando, Fla.)Cbl-b-deficient mice express alterations in trafficking-related molecules but retain sensitivity to the multiple sclerosis therapeutic agent, FTY720.PMC4420730AI097375R01 AI097375RG4070B7/2Anstadt EJClark RBFujiwara MKhanna KMfalseCbl-b-deficient mice express alterations in trafficking-related molecules but retain sensitivity to the multiple sclerosis therapeutic agent, FTY720.The variable response to therapy in multiple sclerosis (MS) suggests a need for personalized approaches based on individual genetic differences. GWAS have linked CBLB gene polymorphisms with MS and recent evidence demonstrated that these polymorphisms can be associated with abnormalities in T cell function and response to interferon-β therapy. Cbl-b is an E3 ubiquitin ligase that regulates T cell activation and Cbl-b-deficient (Cbl-b(-/-)) mice show T cell abnormalities described in MS patients. We now show that Cbl-b(-/-) T cells demonstrate significant lymph node trafficking abnormalities. We thus asked whether the MS-approved drug, FTY720, postulated to trap T cells in lymphoid tissues, is less effective in the context of Cbl-b dysfunction. We now report that FTY720 significantly inhibi2015-01-01T00:00:00Z2015 May2026-04-07T19:28:40.162Z2019-03-27T01:51:03ZS-EPMC44207302582923310.1016/j.clim.2015.03.018