Abstract
FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby preventing their antigen-activated T cell egress to sites of inflammation. FTY720 is highly effective in inhibiting autoimmunity in various animal models. However, there is little known about how FTY720 controls the migration property of memory T cells. Here, we demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of lamina propria (LP) colitogenic effector memory CD4+ T cells (TEM cells; CD45RB lowCD44highCD62L-) into severe combined immunodeficiency (SCID) mice and suppresses interferon-γ, interleukin-2, and tumor necrosis factor-α production by LP CD4+ T cells. The numbers of spleen, peripheral blood, mesenteric lymph node, and LP CD4 + T cells in FTY720-treated mice were significantly reduced compared with those in control mice. Notably, LP CD4 TEM cells as well as splenic CD4+CD45RBhigh T cells expressed several spingosine-1-phosphate receptors that are targets for FTY720. Furthermore, FTY720 also prevented the development of colitis induced by the adoptive transfer of splenic CD4+CD45RBhigh T cells into SCID mice. Collectively, the present data indicate that FTY720 treatment may offer the potential not only to prevent the onset of disease but also to treat memory T cell-mediated autoimmune diseases including inflammatory bowel diseases.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 291 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2006 |
| Externally published | Yes |
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Keywords
- I cell
- Migration
- Therapy
ASJC Scopus subject areas
- Gastroenterology
- Physiology
Cite this
FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis. / Fujii, R.; Kanai, Takanori; Nemoto, Y.; Makita, S.; Oshima, S.; Okamoto, R.; Tsuchiya, K.; Totsuka, T.; Watanabe, M.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 291, No. 2, 2006.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis
AU - Fujii, R.
AU - Kanai, Takanori
AU - Nemoto, Y.
AU - Makita, S.
AU - Oshima, S.
AU - Okamoto, R.
AU - Tsuchiya, K.
AU - Totsuka, T.
AU - Watanabe, M.
PY - 2006
Y1 - 2006
N2 - FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby preventing their antigen-activated T cell egress to sites of inflammation. FTY720 is highly effective in inhibiting autoimmunity in various animal models. However, there is little known about how FTY720 controls the migration property of memory T cells. Here, we demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of lamina propria (LP) colitogenic effector memory CD4+ T cells (TEM cells; CD45RB lowCD44highCD62L-) into severe combined immunodeficiency (SCID) mice and suppresses interferon-γ, interleukin-2, and tumor necrosis factor-α production by LP CD4+ T cells. The numbers of spleen, peripheral blood, mesenteric lymph node, and LP CD4 + T cells in FTY720-treated mice were significantly reduced compared with those in control mice. Notably, LP CD4 TEM cells as well as splenic CD4+CD45RBhigh T cells expressed several spingosine-1-phosphate receptors that are targets for FTY720. Furthermore, FTY720 also prevented the development of colitis induced by the adoptive transfer of splenic CD4+CD45RBhigh T cells into SCID mice. Collectively, the present data indicate that FTY720 treatment may offer the potential not only to prevent the onset of disease but also to treat memory T cell-mediated autoimmune diseases including inflammatory bowel diseases.
AB - FTY720, a sphingosine-derived immunomodulator, causes immunosuppression via enhancement of lymphocyte sequestration into secondary lymphoid organs, thereby preventing their antigen-activated T cell egress to sites of inflammation. FTY720 is highly effective in inhibiting autoimmunity in various animal models. However, there is little known about how FTY720 controls the migration property of memory T cells. Here, we demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of lamina propria (LP) colitogenic effector memory CD4+ T cells (TEM cells; CD45RB lowCD44highCD62L-) into severe combined immunodeficiency (SCID) mice and suppresses interferon-γ, interleukin-2, and tumor necrosis factor-α production by LP CD4+ T cells. The numbers of spleen, peripheral blood, mesenteric lymph node, and LP CD4 + T cells in FTY720-treated mice were significantly reduced compared with those in control mice. Notably, LP CD4 TEM cells as well as splenic CD4+CD45RBhigh T cells expressed several spingosine-1-phosphate receptors that are targets for FTY720. Furthermore, FTY720 also prevented the development of colitis induced by the adoptive transfer of splenic CD4+CD45RBhigh T cells into SCID mice. Collectively, the present data indicate that FTY720 treatment may offer the potential not only to prevent the onset of disease but also to treat memory T cell-mediated autoimmune diseases including inflammatory bowel diseases.
KW - I cell
KW - Migration
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=33745767310&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745767310&partnerID=8YFLogxK
U2 - 10.1152/ajpgi.00496.2005
DO - 10.1152/ajpgi.00496.2005
M3 - Article
VL - 291
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 2
ER -