Signal regulatory protein α regulates the homeostasis of T lymphocytes in the spleen.
Signal regulatory protein α regulates the homeostasis of T lymphocytes in the spleen.
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DOI：
10.4049/jimmunol.1100528
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发表时间：
2011-07-01
期刊：
影响因子：
--
通讯作者：
Matozaki T
中科院分区：
文献类型：
--
作者：
Sato-Hashimoto M;Saito Y;Ohnishi H;Iwamura H;Kanazawa Y;Kaneko T;Kusakari S;Kotani T;Mori M;Murata Y;Okazawa H;Ware CF;Oldenborg PA;Nojima Y;Matozaki T
次级淋巴器官中淋巴滤泡的形成及其动态平衡的分子基础尚不清楚。信号调节蛋白α(Sirpα)是一种主要在树突状细胞或巨噬细胞中表达的Ig超家族蛋白，它通过与另一种Ig超家族蛋白CD47相互作用来介导细胞-细胞信号转导。在这项研究中，我们发现，与野生型小鼠相比，携带突变(MT)Sirpα的小鼠脾中T细胞区的大小和CD_4+T细胞的数量显著减少。此外，SirpαMT小鼠脾中CCL19和CCL21以及IL-7的表达显著减少，而IL-7被认为是T细胞区发育或内稳态的重要因素。利用骨髓嵌合体，我们发现造血型Sirpα对T细胞区的发育以及CCL19和CCL21在脾中的表达起着重要的作用。淋巴毒素及其受体β受体的表达以及对淋巴毒素β受体刺激的体内反应也在SirpαMT小鼠的脾中降低。CD47基因缺陷小鼠也表现出与SirpαMT小鼠相似的表型。这些数据表明，Sirpα及其配体CD47对于T细胞在脾中的稳态稳态是必不可少的。
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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影响因子：
11.4
作者：
Inagaki, K;Yamao, T;Kasuga, M
通讯作者：
Kasuga, M
影响因子：
32.4
作者：
Dejardin, E;Droin, NM;Green, DR
通讯作者：
Green, DR
DOI：
10.1084/jem.194.4.541
发表时间：
2001-08-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blazar BR;Lindberg FP;Ingulli E;Panoskaltsis-Mortari A;Oldenborg PA;Iizuka K;Yokoyama WM;Taylor PA
通讯作者：
Taylor PA
影响因子：
15.3
作者：
Ngo, V N;Cornall, R J;Cyster, J G
通讯作者：
Cyster, J G
DOI：
10.1084/jem.186.8.1223
发表时间：
1997-10-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brocker T
通讯作者：
Brocker T