An additional role of FTY720 in chronic colitis

Abstract

  FTY720 is a sphingosine-1-phosphate receptor modulator, which inhibits T-cell egress from lymph nodes, thereby prevents pathogenic T cells from migrating towards disease sites. In inflammatory bowel diseases, it is thought that colitogenic memory CD4⁺ T cells are intermittently reactivated in regional lymphoid organs, and return to inflammatory tissues. Little is known about how FTY720 controls the migration property of memory T cells and whether FTY720 could control the trafficking of T cells without the presence of lymphoid tissues. First, we here demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of colitogenic lamina propria effector-memory CD4⁺ T (T_EM) cells into SCID mice. Next, We demonstrated that FTY720 treatment suppresses the recirculation of CD4⁺ T cells in splenectomized lymphotoxin-α^−/− mice that lack lymph nodes and spleen. Cell number of CD4⁺ T cells was markedly decreased in peripheral blood of FTY720-treated mice, but conversely increased in bone marrow. Notably, FTY720 treatment prevented the development of colitis induced by transfer of colitogenic T_EM cells into SPX LT-a^−/− x RAG-2^−/− mice. Collectively, the present data indicate that FTY720 treatment may offer an additional role to direct trafficking of CD4⁺ T cells in BM, resulting in the prevention of memory T cell-mediated diseases including inflammatory bowel diseases.