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


ABSTRACT: The molecular basis for formation of lymphoid follicle and its homeostasis in the secondary lymphoid organs remains unclear. Signal regulatory protein ? (SIRP?), 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) SIRP? 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 SIRP? MT mice. By the use of bone marrow chimera, we found that hematopoietic SIRP? 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 ? receptor, as well as the in vivo response to lymphotoxin ? receptor stimulation were also decreased in the spleen of SIRP? MT mice. CD47-deficient mice also manifested phenotypes similar to SIRP? MT mice. These data suggest that SIRP? as well as its ligand CD47 are thus essential for steady-state homeostasis of T cells in the spleen.

SUBMITTER: Sato-Hashimoto M 

PROVIDER: S-EPMC3492956 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

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