Watford Wendy T, Li Denise, Agnello Davide, Durant Lydia, Yamaoka Kunihiro, Yao Zheng Ju, Ahn Hyun-Jong, Cheng Tammy P, Hofmann Sigrun R, Cogliati Tiziana, Chen Amy, Hissong Bruce D, Husa Matthew R, Schwartzberg Pamela, O'Shea John J, Gadina Massimo
LCBS-MIIB-NIAMS-NIH, Bldg. 10, Room 9N256, MSC-1820, 10 Center Dr., Bethesda, MD 20892-1820, USA.
Mol Cell Biol. 2006 Sep;26(17):6623-32. doi: 10.1128/MCB.02460-05.
Cybr (also known as Cytip, CASP, and PSCDBP) is an interleukin-12-induced gene expressed exclusively in hematopoietic cells and tissues that associates with Arf guanine nucleotide exchange factors known as cytohesins. Cybr levels are dynamically regulated during T-cell development in the thymus and upon activation of peripheral T cells. In addition, Cybr is induced in activated dendritic cells and has been reported to regulate dendritic cell (DC)-T-cell adhesion. Here we report the generation and characterization of Cybr-deficient mice. Despite the selective expression in hematopoietic cells, there was no intrinsic defect in T- or B-cell development or function in Cybr-deficient mice. The adoptive transfer of Cybr-deficient DCs showed that they migrated efficiently and stimulated proliferation and cytokine production by T cells in vivo. However, competitive stem cell repopulation experiments showed a defect in the abilities of Cybr-deficient T cells to develop in the presence of wild-type precursors. These data suggest that Cybr is not absolutely required for hematopoietic cell development or function, but stem cells lacking Cybr are at a developmental disadvantage compared to wild-type cells. Collectively, these data demonstrate that despite its selective expression in hematopoietic cells, the role of Cybr is limited or largely redundant. Previous in vitro studies using overexpression or short interfering RNA inhibition of the levels of Cybr protein appear to have overestimated its immunological role.
Cybr（也称为Cytip、CASP和PSCDBP）是一种白细胞介素-12诱导基因，仅在造血细胞和组织中表达，它与一种名为细胞黏附素的Arf鸟嘌呤核苷酸交换因子相关联。Cybr水平在胸腺中T细胞发育过程以及外周T细胞激活时受到动态调节。此外，Cybr在活化的树突状细胞中被诱导表达，并且据报道它可调节树突状细胞（DC）与T细胞的黏附。在此，我们报告了Cybr基因缺陷小鼠的产生及特征。尽管Cybr在造血细胞中选择性表达，但Cybr基因缺陷小鼠的T细胞或B细胞发育及功能并无内在缺陷。Cybr基因缺陷的树突状细胞的过继转移显示，它们在体内能高效迁移并刺激T细胞增殖及产生细胞因子。然而，竞争性干细胞再增殖实验表明，在存在野生型前体细胞的情况下，Cybr基因缺陷的T细胞发育能力存在缺陷。这些数据表明，造血细胞发育或功能并非绝对需要Cybr，但与野生型细胞相比，缺乏Cybr的干细胞在发育上处于劣势。总体而言，这些数据表明，尽管Cybr在造血细胞中选择性表达，但其作用有限或在很大程度上是冗余的。先前使用过表达或短干扰RNA抑制Cybr蛋白水平的体外研究似乎高估了其免疫作用。
