[An additional role of FTY720 in chronic colitis].
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-alpha(-/-) 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.
Fujii
Toshimitsu
T
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University.
Watanabe
Mamoru
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy / Q000276:immunology*; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D011409:Propylene Glycols / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine