Istituto Nazionale Genetica Molecolare, Milano, Italy.
Immunol Rev. 2013 May;253(1):82-96. doi: 10.1111/imr.12055.
CD4(+) T lymphocytes orchestrate adaptive immune responses by differentiating into various subsets of effector T cells such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells. These subsets have been generally described by master transcription factors that dictate the expression of cytokines and receptors, which ultimately define lymphocyte effector functions. However, the view of T-lymphocyte subsets as stable and terminally differentiated lineages has been challenged by increasing evidence of functional plasticity within CD4(+) T-cell subsets, which implies flexible programming of effector functions depending on time and space of T-cell activation. An outstanding question with broad basic and traslational implications relates to the mechanisms, besides transcriptional regulation, which define the plasticity of effector functions. In this study, we discuss the emerging role of regulatory non-coding RNAs in T-cell differentiation and plasticity. Not only microRNAs have been proven to be important for CD4(+) T-cell differentiation, but it is also likely that the overall T-cell functioning is the result of a multilayered network composed by coding RNAs as well as by short and long non-coding RNAs. The integrated study of all the nodes of this network will provide a comprehensive view of the molecular mechanisms underlying T-cell functions in health and disease.
CD4(+) T 淋巴细胞通过分化为各种效应 T 细胞亚群，如 T 辅助 1（Th1）、Th2、Th17 和调节性 T 细胞，来协调适应性免疫反应。这些亚群通常由主转录因子描述，主转录因子决定细胞因子和受体的表达，最终定义淋巴细胞效应功能。然而，CD4(+) T 细胞亚群作为稳定和终末分化谱系的观点受到了越来越多的证据的挑战，这些证据表明 CD4(+) T 细胞亚群在功能上具有可塑性，这意味着根据 T 细胞激活的时间和空间灵活地编程效应功能。一个具有广泛基础和转化意义的突出问题涉及到除转录调控之外，定义效应功能可塑性的机制。在这项研究中，我们讨论了调节性非编码 RNA 在 T 细胞分化和可塑性中的新兴作用。不仅 microRNAs 已被证明对 CD4(+) T 细胞分化很重要，而且很可能整个 T 细胞的功能是由编码 RNA 以及短链和长链非编码 RNA 组成的多层网络的结果。对这个网络的所有节点进行综合研究将提供对 T 细胞在健康和疾病中功能的分子机制的全面了解。
