Src homology 2-containing 5-inositol phosphatase (SHIP) suppresses an early stage of lymphoid cell development through elevated interleukin-6 production by myeloid cells in bone marrow.
Src homology 2-containing 5-inositol phosphatase (SHIP) suppresses an early stage of lymphoid cell development through elevated interleukin-6 production by myeloid cells in bone marrow.
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SRC同源性2含2-氨基醇磷酸酶（Ship）通过骨髓中髓样细胞的介绍介导的白介素-6产生的淋巴样细胞发育的早期阶段。
DOI：
10.1084/jem.20031193
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发表时间：
2004-01-19
影响因子：
15.3
通讯作者：
Coggeshall, KM
中科院分区：
文献类型：
--
作者：
Nakamura, K;Kouro, T;Kincade, PW;Malykhin, A;Maeda, K;Coggeshall, KM
含有 Src 同源 (SH)2 的肌醇 5-磷酸酶 (SHIP) 通过抑制性免疫受体负调节多种免疫反应。在SHIP−/−动物中，我们发现骨髓中早期淋巴祖细胞的数量显着减少，并伴有骨髓细胞的扩张。我们开发了一个使用造血祖细胞的体外系统，再现了 SHIP−/− 小鼠的体内表型。当与 SHIP−/− 小鼠的细胞共培养时，从野生型小鼠中分离的谱系阴性骨髓 (Lin−) 细胞未能分化为 B 细胞。此外，SHIP−/− Lin− 细胞的培养上清液抑制了野生型谱系阴性细胞的 B 谱系扩增，表明存在抑制性细胞因子。 SHIP−/− Lin− 细胞比野生型 Lin− 细胞含有更多的 IL-6 转录物，中和性抗 IL-6 抗体挽救了 SHIP−/− Lin− 细胞上清液抑制的 B 谱系扩张。最后，我们发现将重组IL-6添加到野生型Lin−骨髓细胞培养物中再现了SHIP−/−骨髓培养物的表型：抑制B细胞发育和骨髓细胞扩增。结果表明，IL-6 是一种重要的调节细胞因子，可以抑制 B 谱系分化并驱动骨髓中过度的骨髓发育。
The Src homology (SH)2–containing inositol 5-phosphatase (SHIP) negatively regulates a variety of immune responses through inhibitory immune receptors. In SHIP−/− animals, we found that the number of early lymphoid progenitors in the bone marrow was significantly reduced and accompanied by expansion of myeloid cells. We exploited an in vitro system using hematopoietic progenitors that reproduced the in vivo phenotype of SHIP−/− mice. Lineage-negative marrow (Lin−) cells isolated from wild-type mice failed to differentiate into B cells when cocultured with those of SHIP−/− mice. Furthermore, culture supernatants of SHIP−/− Lin− cells suppressed the B lineage expansion of wild-type lineage-negative cells, suggesting the presence of a suppressive cytokine. SHIP−/− Lin− cells contained more IL-6 transcripts than wild-type Lin− cells, and neutralizing anti–IL-6 antibody rescued the B lineage expansion suppressed by the supernatants of SHIP−/− Lin− cells. Finally, we found that addition of recombinant IL-6 to cultures of wild-type Lin− bone marrow cells reproduced the phenotype of SHIP−/− bone marrow cultures: suppression of B cell development and expansion of myeloid cells. The results identify IL-6 as an important regulatory cytokine that can suppress B lineage differentiation and drive excessive myeloid development in bone marrow.
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DOI：
10.1084/jem.187.1.79
发表时间：
1998-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lin Q;Dong C;Cooper MD
通讯作者：
Cooper MD
影响因子：
15.3
作者：
Allman, D;Li, J;Hardy, RR
通讯作者：
Hardy, RR
影响因子：
11.4
作者：
Huber, M;Helgason, CD;Krystal, G
通讯作者：
Krystal, G
影响因子：
10.5
作者：
Liu, QR;Sasaki, T;Penninger, JM
通讯作者：
Penninger, JM
影响因子：
32.4
作者：
Igarashi, H;Gregory, SC;Kincade, PW
通讯作者：
Kincade, PW