Cbl-b-deficient mice express alterations in trafficking-related molecules but retain sensitivity to the multiple sclerosis therapeutic agent, FTY720
Copyright policy )Cbl-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 inhibits EAE in Cbl-b(-/-) mice. Our results newly document a role for Cbl-b in T cell trafficking but suggest nevertheless that MS patients with Cbl-b abnormalities may still be excellent candidates for FTY720 treatment.
- University of Connecticut Health Center United States
Homeodomain Proteins, Mice, Knockout, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Fingolimod Hydrochloride, T-Lymphocytes, Lymphocyte Activation, Adoptive Transfer, Mice, Cell Movement, Propylene Glycols, Sphingosine, Animals, Lymph Nodes, Proto-Oncogene Proteins c-cbl, Immunosuppressive Agents, Adaptor Proteins, Signal Transducing
Homeodomain Proteins, Mice, Knockout, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Fingolimod Hydrochloride, T-Lymphocytes, Lymphocyte Activation, Adoptive Transfer, Mice, Cell Movement, Propylene Glycols, Sphingosine, Animals, Lymph Nodes, Proto-Oncogene Proteins c-cbl, Immunosuppressive Agents, Adaptor Proteins, Signal Transducing
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