Department of Immunology, Faculty of Medicine, University of Debrecen, 1 Egyetem Square, H-4032 Debrecen, Hungary.
Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, 1 Egyetem Square, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2021 Jan 28;22(3):1316. doi: 10.3390/ijms22031316.
Cells utilize a diverse repertoire of cell surface and intracellular receptors to detect exogenous or endogenous danger signals and even the changes of their microenvironment. However, some cytosolic NOD-like receptors (NLR), including NLRX1, serve more functions than just being general pattern recognition receptors. The dynamic translocation between the cytosol and the mitochondria allows NLRX1 to interact with many molecules and thereby to control multiple cellular functions. As a regulatory NLR, NLRX1 fine-tunes inflammatory signaling cascades, regulates mitochondria-associated functions, and controls metabolism, autophagy and cell death. Nevertheless, literature data are inconsistent and often contradictory regarding its effects on individual cellular functions. One plausible explanation might be that the regulatory effects of NLRX1 are highly cell type specific and the features of NLRX1 mediated regulation might be determined by the unique functional activity or metabolic profile of the given cell type. Here we review the cell type specific actions of NLRX1 with a special focus on cells of the immune system. NLRX1 has already emerged as a potential therapeutic target in numerous immune-related diseases, thus we aim to highlight which regulatory properties of NLRX1 are manifested in disease-associated dominant immune cells that presumably offer promising therapeutic solutions to treat these disorders.
细胞利用多样化的细胞表面和细胞内受体来检测外源性或内源性危险信号，甚至检测其微环境的变化。然而，一些细胞质核苷酸结合寡聚化结构域样受体（NLR），包括 NLRX1，其功能不仅仅是作为一般的模式识别受体。NLRX1 在细胞质和线粒体之间的动态易位使其能够与许多分子相互作用，从而控制多种细胞功能。作为一种调节性 NLR，NLRX1 可以精细调节炎症信号级联反应、调节与线粒体相关的功能，并控制代谢、自噬和细胞死亡。然而，关于其对单个细胞功能的影响，文献数据并不一致，且常常相互矛盾。一个合理的解释可能是 NLRX1 的调节作用具有高度的细胞类型特异性，并且 NLRX1 介导的调节特征可能由特定细胞类型的独特功能活性或代谢特征决定。在这里，我们重点讨论免疫系统细胞，综述 NLRX1 的细胞类型特异性作用。NLRX1 已经成为许多与免疫相关疾病的潜在治疗靶点，因此，我们旨在强调 NLRX1 的哪些调节特性在与疾病相关的主导免疫细胞中表现出来，这些特性可能为治疗这些疾病提供有希望的治疗方案。
