Signal regulatory protein α regulates the homeostasis of T lymphocytes in the spleen.

نویسندگان

  • Miho Sato-Hashimoto
  • Yasuyuki Saito
  • Hiroshi Ohnishi
  • Hiroko Iwamura
  • Yoshitake Kanazawa
  • Tetsuya Kaneko
  • Shinya Kusakari
  • Takenori Kotani
  • Munemasa Mori
  • Yoji Murata
  • Hideki Okazawa
  • Carl F Ware
  • Per-Arne Oldenborg
  • Yoshihisa Nojima
  • Takashi Matozaki
چکیده

The molecular basis for formation of lymphoid follicle and its homeostasis in the secondary lymphoid organs remains unclear. Signal regulatory protein α (SIRPα), an Ig superfamily protein that is predominantly expressed in dendritic cells or macrophages, mediates cell-cell signaling by interacting with CD47, another Ig superfamily protein. In this study, we show that the size of the T cell zone as well as the number of CD4(+) T cells were markedly reduced in the spleen of mice bearing a mutant (MT) SIRPα that lacks the cytoplasmic region compared with those of wild-type mice. In addition, the expression of CCL19 and CCL21, as well as of IL-7, which are thought to be important for development or homeostasis of the T cell zone, was markedly decreased in the spleen of SIRPα MT mice. By the use of bone marrow chimera, we found that hematopoietic SIRPα is important for development of the T cell zone as well as the expression of CCL19 and CCL21 in the spleen. The expression of lymphotoxin and its receptor, lymphotoxin β receptor, as well as the in vivo response to lymphotoxin β receptor stimulation were also decreased in the spleen of SIRPα MT mice. CD47-deficient mice also manifested phenotypes similar to SIRPα MT mice. These data suggest that SIRPα as well as its ligand CD47 are thus essential for steady-state homeostasis of T cells in the spleen.

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عنوان ژورنال:
  • Journal of immunology

دوره 187 1  شماره 

صفحات  -

تاریخ انتشار 2011