Larkin Bridget, Ilyukha Vladimir, Sorokin Maxim, Buzdin Anton, Vannier Edouard, Poltorak Alexander
Program in Immunology, Sackler Graduate School, Tufts University, Boston, MA 02111.
Petrozavodsk State University, 185910 Petrozavodsk, Republic of Karelia, Russia.
J Immunol. 2017 Jul 15;199(2):397-402. doi: 10.4049/jimmunol.1601999. Epub 2017 Jun 14.
Stimulator of interferon genes (STING) was initially described as a sensor of intracellular bacterial and viral DNA and a promising adjuvant target in innate immune cells; more recently STING has also been shown to detect endogenous DNA and play a role in tumor immunity and autoimmune disease development. Thus far STING has been studied in macrophages and dendritic cells. In this study, to our knowledge we provide the first evidence of STING activation in T cells, in which STING agonists not only provoke type I IFN production and IFN-stimulated gene expression, mirroring the response of innate cells, but are also capable of activating cell stress and death pathways. Our results suggest a re-evaluation of STING agonist-based therapies may be necessary to identify the possible effects on the T cell compartment. Conversely, the effects of STING on T cells could potentially be harnessed for therapeutic applications.
干扰素基因刺激蛋白(STING)最初被描述为细胞内细菌和病毒DNA的传感器以及先天免疫细胞中有前景的佐剂靶点;最近还发现STING能检测内源性DNA,并在肿瘤免疫和自身免疫性疾病发展中发挥作用。到目前为止,对STING的研究主要集中在巨噬细胞和树突状细胞。在本研究中,据我们所知,我们首次提供了T细胞中STING激活的证据,其中STING激动剂不仅能引发I型干扰素产生和干扰素刺激基因表达,这与先天免疫细胞的反应相似,还能够激活细胞应激和死亡途径。我们的结果表明,可能有必要重新评估基于STING激动剂的疗法,以确定其对T细胞区室的潜在影响。相反,STING对T细胞的作用也可能被用于治疗应用。