FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow

Toshimitsu Fujii, Takayuki Tomita, Takanori Kanai, Yasuhiro Nemoto, Teruji Totsuka, Naoya Sakamoto, Tetsuya Nakamura, Kiichiro Tsuchiya, Ryuichi Okamoto, Mamoru Watanabe

Research output: Contribution to journalArticle

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Abstract

2-Amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride (FTY720) suppresses T-cell egress from LN, thereby preventing pathogenic T cells from migrating toward disease sites. However, little is known about whether FTY720 could control the trafficking of T cells without the presence of lymphoid tissues. Here we demonstrate that FTY720 treatment suppresses the recirculation of CD4+ T cells in splenectomized (SPX) lymphotoxin-α-/- (LT-α -/-) mice that lack LN and spleen, as shown by peripheral blood (PB) lymphopenia in FTY720-treated SPX LT-α -/- mice. In a short-term transfer experiment, the cell number of transferred Ly5.1+CD4+ T cells recovered from host FTY720-treated SPX LT-α-/- mice (Ly5.2+) was markedly decreased in PB, but conversely increased in BM. Notably, FTY720 treatment prevented the development of colitis that is otherwise induced in untreated SPX LT-α -/- x RAG-2-/- mice upon transfer of colitic lamina propria CD4+ T cells. In such mice, the number of CD4+ T cells in PB or lamina propria of FTY720-treated SPX LT-α-/- x RAG-2-/- recipients was significantly reduced, but that in the BM was significantly increased as compared with untreated control mice. Altogether, the present results indicate that FTY720 treatment may offer an additional role to direct trafficking of CD4+ T cells in BM, resulting in the prevention of colitis.

Original languageEnglish
Pages (from-to)3290-3303
Number of pages14
JournalEuropean Journal of Immunology
Volume38
Issue number12
DOIs
Publication statusPublished - 2008

Fingerprint

Colitis
Bone Marrow
T-Lymphocytes
Lymphotoxin-alpha
Mucous Membrane
Fingolimod Hydrochloride
Lymphopenia
Lymphoid Tissue
Spleen
Cell Count

Keywords

  • Chronic colitis
  • Colitogenic CD4 T cells
  • FTY720
  • Inflammatory bowel disease
  • Mucosal immunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow. / Fujii, Toshimitsu; Tomita, Takayuki; Kanai, Takanori; Nemoto, Yasuhiro; Totsuka, Teruji; Sakamoto, Naoya; Nakamura, Tetsuya; Tsuchiya, Kiichiro; Okamoto, Ryuichi; Watanabe, Mamoru.

In: European Journal of Immunology, Vol. 38, No. 12, 2008, p. 3290-3303.

Research output: Contribution to journalArticle

Fujii, T, Tomita, T, Kanai, T, Nemoto, Y, Totsuka, T, Sakamoto, N, Nakamura, T, Tsuchiya, K, Okamoto, R & Watanabe, M 2008, 'FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow', European Journal of Immunology, vol. 38, no. 12, pp. 3290-3303. https://doi.org/10.1002/eji.200838359
Fujii, Toshimitsu ; Tomita, Takayuki ; Kanai, Takanori ; Nemoto, Yasuhiro ; Totsuka, Teruji ; Sakamoto, Naoya ; Nakamura, Tetsuya ; Tsuchiya, Kiichiro ; Okamoto, Ryuichi ; Watanabe, Mamoru. / FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow. In: European Journal of Immunology. 2008 ; Vol. 38, No. 12. pp. 3290-3303.
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AU - Fujii, Toshimitsu

AU - Tomita, Takayuki

AU - Kanai, Takanori

AU - Nemoto, Yasuhiro

AU - Totsuka, Teruji

AU - Sakamoto, Naoya

AU - Nakamura, Tetsuya

AU - Tsuchiya, Kiichiro

AU - Okamoto, Ryuichi

AU - Watanabe, Mamoru

PY - 2008

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AB - 2-Amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride (FTY720) suppresses T-cell egress from LN, thereby preventing pathogenic T cells from migrating toward disease sites. However, little is known about whether FTY720 could control the trafficking of T cells without the presence of lymphoid tissues. Here we demonstrate that FTY720 treatment suppresses the recirculation of CD4+ T cells in splenectomized (SPX) lymphotoxin-α-/- (LT-α -/-) mice that lack LN and spleen, as shown by peripheral blood (PB) lymphopenia in FTY720-treated SPX LT-α -/- mice. In a short-term transfer experiment, the cell number of transferred Ly5.1+CD4+ T cells recovered from host FTY720-treated SPX LT-α-/- mice (Ly5.2+) was markedly decreased in PB, but conversely increased in BM. Notably, FTY720 treatment prevented the development of colitis that is otherwise induced in untreated SPX LT-α -/- x RAG-2-/- mice upon transfer of colitic lamina propria CD4+ T cells. In such mice, the number of CD4+ T cells in PB or lamina propria of FTY720-treated SPX LT-α-/- x RAG-2-/- recipients was significantly reduced, but that in the BM was significantly increased as compared with untreated control mice. Altogether, the present results indicate that FTY720 treatment may offer an additional role to direct trafficking of CD4+ T cells in BM, resulting in the prevention of colitis.

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