Kaplan Mark H, Sehra Sarita, Chang Hua-Chen, O'Malley John T, Mathur Anubhav N, Bruns Heather A
Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Blood. 2007 Dec 15;110(13):4367-9. doi: 10.1182/blood-2007-06-098244. Epub 2007 Sep 18.
Signal transducer and activator of transcription 6 (STAT6) is critical for IL-4 and IL-13 responses, and necessary for the normal development of Th2 cells. We previously generated mice that express a constitutively active STAT6 (STAT6VT) under control of the CD2 locus control region, which directs expression to the T-cell compartment. We now describe that a small proportion of these mice (~5%) develop a spontaneous lymphoproliferative disease (LPD) that results in dramatic splenomegaly. The cell populations observed in the LPD spleens can be divided into 2 categories, those that are composed of mixed lineage cells and those that are predominantly T cells with a phenotype similar to that in autoimmune lymphoproliferative syndrome (ALPS) patients. These data suggest that while active STAT6 is not a transforming factor, expression in T cells predisposes toward the development of lymphoproliferative disorders.
信号转导及转录激活因子6（STAT6）对白细胞介素-4（IL-4）和白细胞介素-13（IL-13）反应至关重要，是辅助性T细胞2（Th2）正常发育所必需的。我们之前构建了在CD2基因座控制区控制下表达组成型活性STAT6（STAT6VT）的小鼠，该基因座控制区将表达导向T细胞区室。我们现在描述，这些小鼠中有一小部分（约5%）会发生自发性淋巴细胞增殖性疾病（LPD），导致脾脏显著肿大。在LPD脾脏中观察到的细胞群体可分为两类，一类由混合谱系细胞组成，另一类主要是具有与自身免疫性淋巴细胞增殖综合征（ALPS）患者相似表型的T细胞。这些数据表明，虽然活性STAT6不是转化因子，但在T细胞中的表达易导致淋巴细胞增殖性疾病的发生。
