Eos (lkzf4) is a member of the Ikaros family of transcription factors and is preferentially expressed in T-regulatory (Treg) cells. However, the role of Eos in Treg function is controversial. One study using siRNA knock down of Eos demonstrated that it was critical for Treg suppressor function. In contrast, Treg from mice with a global deficiency of Eos had normal Treg function in vitro and in vivo. To further dissect the function of Eos in Tregs, we generated mice with a conditional knock out of Eos in Treg cells (lkzf4fl/fl X Foxp3YFP-cre, Eos cKO). Deletion of Eos in Treg resulted in activation of CD4+Foxp3- and CD8+ T cells at the age of 3 months, cellular infiltration in non-lymphoid tissues, hyperglobulinemia, and anti-nuclear antibodies. While Tregs from Eos cKO mice displayed normal suppressive function in vitro, Eos cKO mice developed severe Experimental Autoimmune Encephalomyletis (EAE) following immunization with myelin oligodendrocyte glycoprotein (MOG) and Eos cKO Treg were unable to suppress Inflammatory Bowel Disease (IBD). Eos cKO mice had decreased growth of the transplantable murine adenocarcinoma MC38 tumor accompanied by enhanced IFN-γ/TNF-α production by CD8+ T cells in tumor draining lymph nodes. Mice with a global deficiency of Eos or a deficiency of Eos only in T cells developed autoimmunity at a much older age (12 months or 7-8 months, respectively). Taken together, Eos appears to play an essential role in multiple aspects of Treg suppressor function, but also plays an as yet unknown role in the function of CD4+Foxp3- and CD8+ T cells and potentially in non-T cells.

中文翻译：

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T调节细胞中Eos（Ikzf4）的选择性缺失导致抑制功能的丧失和全身性自身免疫的发展。

Eos（lkzf4）是Ikaros转录因子家族的成员，并优先在T调节（Treg）细胞中表达。然而，Eos在Treg功能中的作用是有争议的。一项使用siRNA敲除Eos的研究表明，它对Treg抑制子功能至关重要。相反，来自Eos总体缺乏的小鼠的Treg在体外和体内均具有正常的Treg功能。为了进一步剖析Eos在Treg中的功能，我们产生了在Treg细胞（lkzf4fl / fl X Foxp3YFP-cre，Eos cKO）中有条件地敲除Eos的小鼠。Treg中Eos的缺失导致3个月大时CD4 + Foxp3-和CD8 + T细胞活化，非淋巴组织中的细胞浸润，高球蛋白血症和抗核抗体。尽管Eos cKO小鼠的Treg在体外显示出正常的抑制功能，Eos cKO小鼠在用髓磷脂少突胶质细胞糖蛋白（MOG）免疫后出现了严重的实验性自身免疫性脑脊髓炎（EAE），Eos cKO Treg无法抑制炎症性肠病（IBD）。Eos cKO小鼠的可移植鼠腺癌MC38肿瘤的生长减少，同时肿瘤引流淋巴结中CD8 + T细胞产生的IFN-γ/TNF-α增强。总体上缺乏Eos或仅在T细胞中缺乏Eos的小鼠在大得多的年龄（分别为12个月或7-8个月）出现了自身免疫。两者合计，Eos似乎在Treg抑制功能的多个方面起着至关重要的作用，但在CD4 + Foxp3-和CD8 + T细胞的功能中以及潜在地在非T细胞的功能中也起着未知的作用。