Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
IRCCS Neuromed, Pozzilli, Italy.
Immunol Rev. 2018 Nov;286(1):148-159. doi: 10.1111/imr.12705.
Immunity to pathogens is ensured through integration of early responses mediated by innate cells and late effector functions taking place after terminal differentiation of adaptive lymphocytes. In this context, innate lymphoid cells (ILCs) and adaptive T cells represent a clear example of how prototypical effector functions, including polarized expression of cytokines and/or cytotoxic activity, can occur with overlapping modalities but different timing. The ability of ILCs to provide early protection relies on their poised epigenetic state, which determines their propensity to quickly respond to cytokines and to activate specific patterns of signal-dependent transcription factors. Cytokines activating the Janus kinases (JAKs) and members of the signal transducer and activator of transcription (STAT) pathway are key regulators of lymphoid development and sustain the processes underlying T-cell activation and differentiation. The role of the JAK/STAT pathway has been recently extended to several aspects of ILC biology. Here, we discuss how JAK/STAT signals affect ILC development and effector functions in the context of immune responses, highlighting the molecular mechanisms involved in regulation of gene expression as well as the potential of targeting the JAK/STAT pathway in inflammatory pathologies.
病原体的免疫是通过先天细胞介导的早期反应和适应性淋巴细胞终末分化后发生的晚期效应功能的整合来保证的。在这方面，先天淋巴细胞 (ILC) 和适应性 T 细胞是一个明显的例子，说明了包括细胞因子的极化表达和/或细胞毒性活性等典型的效应功能如何以重叠的方式发生，但具有不同的时间。ILC 提供早期保护的能力依赖于其预先确定的表观遗传状态，这决定了它们快速响应细胞因子和激活特定信号依赖性转录因子模式的倾向。激活 Janus 激酶 (JAK) 和信号转导和转录激活因子 (STAT) 途径成员的细胞因子是淋巴细胞发育的关键调节剂，并维持 T 细胞激活和分化的过程。JAK/STAT 途径的作用最近已扩展到 ILC 生物学的几个方面。在这里，我们讨论了 JAK/STAT 信号如何影响免疫反应背景下的 ILC 发育和效应功能，强调了参与基因表达调控的分子机制以及靶向 JAK/STAT 途径在炎症性病理中的潜力。
