Brezar Vedran, Tu Wen Juan, Seddiki Nabila
INSERM U955, Équipe 16 and Faculté de Médecine, Université Paris Est , Créteil , France ; Vaccine Research Institute (VRI) , Créteil , France.
Faculty of Education, Science, Technology and Maths, University of Canberra , Canberra, ACT , Australia.
Front Immunol. 2015 Oct 13;6:530. doi: 10.3389/fimmu.2015.00530. eCollection 2015.
One of the major goals in immunology research is to understand the regulatory mechanisms that underpin the rapid switch on/off of robust and efficient effector (Teffs) or regulatory (Tregs) T-cell responses. Understanding the molecular mechanisms underlying the regulation of such responses is critical for the development of effective therapies. T-cell activation involves the engagement of T-cell receptor and co-stimulatory signals, but the subsequent recruitment of serine/threonine-specific protein Kinase C-theta (PKC-θ) to the immunological synapse (IS) is instrumental for the formation of signaling complexes, which ultimately lead to a transcriptional network in T cells. Recent studies demonstrated that major differences between Teffs and Tregs occurred at the IS where its formation induces altered signaling pathways in Tregs. These pathways are characterized by reduced recruitment of PKC-θ, suggesting that PKC-θ inhibits Tregs suppressive function in a negative feedback loop. As the balance of Teffs and Tregs has been shown to be central in several diseases, it was not surprising that some studies revealed that PKC-θ plays a major role in the regulation of this balance. This review will examine recent knowledge on the role of PKC-θ in T-cell transcriptional responses and how this protein can impact on the function of both Tregs and Teffs.
免疫学研究的主要目标之一是了解支撑强大而高效的效应性T细胞(Teffs)或调节性T细胞(Tregs)反应快速开启/关闭的调控机制。了解此类反应调控背后的分子机制对于开发有效疗法至关重要。T细胞活化涉及T细胞受体和共刺激信号的参与,但随后丝氨酸/苏氨酸特异性蛋白激酶C-θ(PKC-θ)募集到免疫突触(IS)对于信号复合物的形成至关重要,而信号复合物最终会导致T细胞中的转录网络。最近的研究表明,Teffs和Tregs之间的主要差异发生在IS处,其形成会诱导Tregs中信号通路的改变。这些通路的特征是PKC-θ的募集减少,这表明PKC-θ在负反馈回路中抑制Tregs的抑制功能。由于Teffs和Tregs的平衡已被证明在几种疾病中至关重要,因此一些研究表明PKC-θ在调节这种平衡中起主要作用也就不足为奇了。本综述将探讨关于PKC-θ在T细胞转录反应中的作用以及该蛋白如何影响Tregs和Teffs功能的最新知识。