Barton Beverly E
Division of Urology, Department of Surgery, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
Expert Opin Ther Targets. 2006 Jun;10(3):459-70. doi: 10.1517/14728222.10.3.459.
Dendritic cells (DCs) control the segue from innate to adaptive immunity. Moreover, depending upon their milieu, DCs can either induce or inhibit immune responses. Whether DCs are immune stimulatory or tolerogenic apparently rests with whether or not the DCs express activated signal transducer and activator of transcription-3 (STAT3), the transcription factor induced by IL-6-like cytokines and IL-10. DCs expressing activated STAT3 produce less IL-12, which results in less effector T cell development. Moreover, DCs expressing activated STAT3 also express the tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase. The kynurenine products of tryptophan catabolism induce T cell apoptosis; this area is of major interest to researchers working on tolerogenic DCs. In various disease models ranging from tumours to autoimmune diseases, administration of STAT3-activating cytokines resulted in attenuation of immune responses. Other corroborating evidence was obtained using conditional STAT3-deficient mice, or mice defective in cytokine signalling. Thus, persistently activating STAT3 in DCs may be a feasible strategy for controlling allograft rejection.
树突状细胞（DCs）控制着从固有免疫到适应性免疫的转变。此外，根据其所处环境，DCs 既可以诱导免疫反应，也可以抑制免疫反应。DCs 是具有免疫刺激作用还是具有免疫耐受性，显然取决于 DCs 是否表达活化的信号转导子和转录激活子 3（STAT3），STAT3 是一种由白细胞介素 6 样细胞因子和白细胞介素 10 诱导产生的转录因子。表达活化 STAT3 的 DCs 产生的白细胞介素 12 较少，这导致效应 T 细胞的发育减少。此外，表达活化 STAT3 的 DCs 还表达色氨酸分解代谢酶吲哚胺 2,3-双加氧酶。色氨酸分解代谢产生的犬尿氨酸可诱导 T 细胞凋亡；这一领域是致力于研究耐受性 DCs 的研究人员主要感兴趣的方面。在从肿瘤到自身免疫性疾病的各种疾病模型中，给予 STAT3 激活细胞因子会导致免疫反应减弱。使用条件性 STAT3 缺陷小鼠或细胞因子信号传导有缺陷的小鼠也获得了其他佐证证据。因此，持续激活 DCs 中的 STAT3 可能是控制同种异体移植排斥反应的一种可行策略。
