Abstract
Abstract FTY720 is the functional analogue of sphingosine and is the first oral treatment for relapsing remitting MS. We investigated the immune regulatory effects of Fingolimod (FTY720) on T cells in Multiple Sclerosis (MS) and controls. FTY720 function by blocking immune cell trafficking and prevents relapses in Multiple Sclerosis. We found that T cells activated in the presence of FTY-720 were less inflammatory with decreased proliferation and cytokines expression. FTY720 treated T cells have decreased expression of granzyme B and induced less neuronal cytotoxicity. We showed, FTY720 treated T cells have unique anti-inflammatory immune gene profile. The anti-inflammatory effect of FTY720 on T cells is dependent upon increased expression of a regulatory transcription factor TCF1 (Transcription factor 1). TCF1 has been previously linked to T- cell differentiation and lineage specification in mice. We show that the TCF1 could regulate human T cell differentiation. Knock down of TCF1 gene expression in human T cells switched anti-inflammatory T cells to pro-inflammatory T cell phenotype. In summary, we showed that FTY720 could regulate human T cells differentiation and its immune regulatory function is dependent upon the expression of regulatory transcription factor TCF1.
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