Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction.
Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction.
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DOI：
10.4049/jimmunol.163.11.5971
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发表时间：
1999-12
影响因子：
4.4
通讯作者：
D. E. Isaksen;H. Baumann;P. Trobridge;A. Farr;S. Levin;S. Ziegler
中科院分区：
文献类型：
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作者：
D. E. Isaksen;H. Baumann;P. Trobridge;A. Farr;S. Levin;S. Ziegler
胸腺基质淋巴细胞生成素（Thymic stromal lymphopoietin，TSLP）是一种新发现的细胞因子，能独特地促进B淋巴细胞向B220+/IgM+未成熟B细胞阶段的增殖。此外，TSLP与相关的细胞因子IL-7共享许多生物学特性。这可以通过以下发现来解释：TSLP和IL-7的受体复合物均含有IL-7 Ra链; IL-7 Ra与IL-7受体复合物中的共同γ链（gammac）和TSLP受体复合物中的独特TSLP-R链配对。虽然TSLP和IL-7都诱导转录因子Stat 5的酪氨酸磷酸化，但只有IL-7介导的信号转导可能与Janus家族激酶（Jaks）的激活有关。由于细胞因子刺激后Stat 5磷酸化通常由Jaks介导，TSLP处理后缺乏Jak活化表明酪氨酸磷酸化Stat 5可能无功能。在此，我们证明，TSLP诱导的功能性Stat 5转录因子，TSLP刺激导致Stat 5-DNA复合物的形成和转录的Stat 5响应基因CIS。我们还表明，TSLP受体复合物的功能重建TSLP-R和IL-7 R α和TSLP介导的信号转导需要Stat 5。此外，TSLP介导的信号传导被细胞因子信号传导抑制因子（SOCS）-1和Tec的激酶缺陷型抑制，但不被Jak 1和Jak 2的激酶缺陷型抑制。
Thymic stromal lymphopoietin (TSLP) is a newly identified cytokine that uniquely promotes B lymphopoiesis to the B220+/IgM+ immature B cell stage. In addition, TSLP shares many biological properties with the related cytokine IL-7. This can be explained by the finding that the receptor complexes for TSLP and IL-7 both contain the IL-7R alpha-chain; IL-7Ralpha is paired with the common gamma-chain (gammac) in the IL-7 receptor complex and the unique TSLP-R chain in the TSLP receptor complex. Although TSLP and IL-7 both induce tyrosine phosphorylation of the transcription factor Stat5, only IL-7-mediated signal transduction could be associated with activation of Janus family kinases (Jaks). Because Stat5 phosphorylation following cytokine stimulation is generally mediated by Jaks, the lack of Jak activation after TSLP treatment suggested the possibility that tyrosine-phosphorylated Stat5 may be nonfunctional. Herein, we demonstrate that TSLP induces a functional Stat5 transcription factor in that TSLP stimulation results in Stat5-DNA complex formation and transcription of the Stat5-responsive gene CIS. We also show that the TSLP receptor complex is functionally reconstituted using TSLP-R and IL-7Ralpha and that TSLP-mediated signal transduction requires Stat5. Moreover, TSLP-mediated signaling is inhibited by suppressor of cytokine signaling (SOCS)-1 and a kinase-deficient version of Tec but not by kinase-deficient forms of Jak1 and Jak2.