Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3
Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3
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DOI：
10.1016/j.molimm.2008.01.024
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Starr, Robyn
中科院分区：
文献类型：
--
作者：
Croom, Hayley A.;Izon, David J.;Starr, Robyn
细胞因子信号对胸腺细胞的分化及其在特定发育阶段的逐步进展起着中心作用。细胞因子信号的强度和持续时间受细胞因子信号转导抑制因子(SOCS)蛋白的调节。SOCS1在胸腺生成后期的作用已被明确，但对其在胸腺生成早期的作用及其近亲SOCS3的功能知之甚少。在这里，我们发现SOCS1和SOCS3都在胸腺生成的早期表达，在双阴性(DN)2和DN3阶段表达一致。我们通过将SOCS缺陷的骨髓细胞与表达Notch配体Delta-like 1(OP9-DL1)的OP9细胞共培养来检测胸腺细胞的分化。缺乏SOCS1的细胞在DN3：DN4的转变过程中被延迟，似乎不能分化为双阳性(DP)胸腺细胞。缺乏SOCS1和SOCS3的细胞受到的影响更严重，并在SOCS1和SOCS3表达一致的DN2阶段表现出较早的T细胞分化障碍。这表明，除了它们特定的角色外，SOCS1和SOCS3在胸腺生成过程中还共享重叠的角色。这是SOCS家族中功能冗余的第一次演示，并揭示了SOCS1和SOCS3在T细胞早期发育的两个重要检查点中的重要作用。(C)2008爱思唯尔有限公司。保留所有权利。
Cytokine signals are central to the differentiation of thymocytes and their stepwise progression through defined developmental stages. The intensity and duration of cytokine signals are regulated by the suppressor of cytokine signalling (SOCS) proteins. A clear role for SOCS1 during the later stages of thymopoiesis has been established, but little is known about its role during early thymopoiesis, nor the function of its closest relative, SOCS3. Here, we find that both SOCS1 and SOCS3 are expressed during early thymopoiesis, with expression coincident during the double negative (DN)2 and DN3 stages. We examined thymocyte differentiation in vitro by co-culture of SOCS-deficient bone marrow cells with OP9 cells expressing the Notch ligand Delta-like1 (OP9-DL1). Cells lacking SOCS1 were retarded at the DN3:DN4 transition and appeared unable to differentiate into double positive (DP) thymocytes. Cells lacking both SOCS1and SOCS3 were more severely affected, and displayed an earlier block in T cell differentiation at DN2, the stage at which expression of SOCS1 and SOCS3 coincides. This indicates that, in addition to their specific roles, SOCS1 and SOCS3 share overlapping roles during thymopoiesis. This is the first demonstration of functional redundancy within the SOCS family, and has uncovered a vital role for SOCS1 and SOCS3 during two important checkpoints in early T cell development. (c) 2008 Elsevier Ltd. All rights reserved.