PDF(Pubmed)
Abstract：
Inflammation control is critical during the innate immune response. Such response is triggered by the detection of molecules originating from pathogens or damaged host cells by pattern-recognition receptors (PRRs). PRRs subsequently initiate intra-cellular signalling through different pathways, resulting in i) the production of inflammatory cytokines, including type I interferon (IFN), and ii) the initiation of a cascade of events that promote both immediate host responses as well as adaptive immune responses. All human PYRIN and HIN-200 domains (PYHIN) protein family members were initially proposed to be PRRs, although this view has been challenged by reports that revealed their impact on other cellular mechanisms. Of relevance here, the human PYHIN factor myeloid nuclear differentiation antigen (MNDA) has recently been shown to directly control the transcription of genes encoding factors that regulate programmed cell death and inflammation. While MNDA is mainly found in the nucleus of leukocytes of both myeloid (neutrophils and monocytes) and lymphoid (B-cell) origin, its subcellular localization has been shown to be modulated in response to genotoxic agents that induce apoptosis and by bacterial constituents, mediators of inflammation. Prior studies have noted the importance of MNDA as a marker for certain forms of lymphoma, and as a clinical prognostic factor for hematopoietic diseases characterized by defective regulation of apoptosis. Abnormal expression of MNDA has also been associated with altered levels of cytokines and other inflammatory mediators. Refining our comprehension of the regulatory mechanisms governing the expression of MNDA and other PYHIN proteins, as well as enhancing our definition of their molecular functions, could significantly influence the management and treatment strategies of numerous human diseases. Here, we review the current state of knowledge regarding PYHIN proteins and their role in innate and adaptive immune responses. Emphasis will be placed on the regulation, function, and relevance of MNDA expression in the control of gene transcription and RNA stability during cell death and inflammation.
摘要：
在先天免疫应答期间,炎症控制是关键的。通过模式识别受体(PRR)检测源自病原体或受损宿主细胞的分子来触发这种应答。PRR随后通过不同的途径启动细胞内信号传导，导致i)炎性细胞因子的产生，包括I型干扰素（IFN），和ii)启动促进即时宿主应答以及适应性免疫应答的事件级联。所有人类PYRIN和HIN-200结构域(PYHIN)蛋白家族成员最初被认为是PRRs,尽管这一观点受到了报道的挑战，这些报道揭示了它们对其他细胞机制的影响。在这里相关的，人类PYHIN因子髓样核分化抗原(MNDA)最近被证明直接控制编码调节程序性细胞死亡和炎症的因子的基因的转录。虽然MNDA主要存在于骨髓（中性粒细胞和单核细胞）和淋巴（B细胞）起源的白细胞的细胞核中，它的亚细胞定位已被显示为响应于诱导细胞凋亡的基因毒性因子和细菌成分而被调节，炎症的介质。先前的研究已经注意到MNDA作为某些形式的淋巴瘤的标志物的重要性，并作为以凋亡调节缺陷为特征的造血疾病的临床预后因子。MNDA的异常表达也与细胞因子和其他炎性介质的水平改变有关。完善我们对MNDA和其他PYHIN蛋白表达调控机制的理解，以及增强我们对它们分子功能的定义，可以显着影响许多人类疾病的管理和治疗策略。这里,我们对PYHIN蛋白及其在先天和适应性免疫反应中的作用进行了综述.重点将放在条例上,函数,以及MNDA表达在细胞死亡和炎症过程中控制基因转录和RNA稳定性中的相关性。
