SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and function

SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and function
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DOI:
10.1128/mcb.24.13.6094-6103.2004
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发表时间:
2004-07-01
影响因子:
5.3
通讯作者:
Alexander, WS
Alexander, WS
中科院分区:
生物学2区
文献类型:
--
作者:
Brender, C;Columbus, R;Alexander, WS

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细胞因子信号转导抑制因子(SOCS)是造血细胞和非造血细胞中细胞因子诱导反应的关键调节因子。SOCS1和SOCS3已被证明可以调节T细胞反应,而其他SOCS家族成员在调节淋巴细胞功能中的作用还不是很清楚。在这里,我们报告了Socs5基因定向中断的小鼠的生成。Socs5(-/-)小鼠出生在正常的孟德尔比例中,健康且有生育能力。我们发现SOCS5在野生型小鼠的原代B和T细胞中表达。然而,在SOCS5缺陷小鼠中没有发现淋巴细胞室的异常。我们在没有SOCS5的情况下检测了抗原和细胞因子诱导的B和T细胞的增殖反应,发现与野生型细胞中的反应没有偏差。因为SOCS5与Th1分化有关,所以我们也研究了SOCS5在T辅助细胞反应中的重要性。出乎意料的是,SOCS5缺陷的CD4T细胞在Th1/Th2分化中没有异常,SOCS5(-/-)小鼠对主要利什曼原虫的感染表现出正常的抵抗力。因此,尽管SOCS5在原代B和T细胞中表达,但对淋巴细胞功能的调节似乎是不必要的。
Suppressors of cytokine signaling (SOCSs) are key regulators of cytokine-induced responses in hematopoietic as well as nonhematopoietic cells. SOCS1 and SOCS3 have been shown to modulate T-cell responses, whereas the roles of other SOCS family members in the regulation of lymphocyte function are less clear. Here, we report the generation of mice with a targeted disruption of the Socs5 gene. Socs5(-/-) mice were born in a normal Mendelian ratio and were healthy and fertile. We found that SOCS5 is expressed in primary B and T cells in wild-type mice. However, no abnormalities in the lymphocyte compartment were seen in SOCS5-deficient mice. We examined antigen- and cytokine-induced proliferative responses in B and T cells in the absence of SOCS5 and found no deviations from the responses seen in wild-type cells. Because SOCS5 has been implicated in Th1 differentiation, we also investigated the importance of SOCS5 in T helper cell responses. Unexpectedly, SOCS5-deficient CD4 T cells showed no abnormalities in Th1/Th2 differentiation and Socs5(-/-) mice showed normal resistance to infection with Leishmania major. Therefore, although SOCS5 is expressed in primary B and T cells, it appears to be dispensable for the regulation of lymphocyte function.