Tumor Immunotherapy Program, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Immunology, Microenvironment and Metastasis Program, The Wistar Institute Cancer Center, Philadelphia, PA, USA.
Mol Aspects Med. 2021 Apr;78:100942. doi: 10.1016/j.mam.2021.100942. Epub 2021 Jan 12.
Nuclear receptors (NRs) are key regulators of innate immune responses and tissue homeostasis. Evidence indicates that NRs significantly impact steady-state immune regulation, uptake and processing of apoptotic cells, tolerance induction, and control of inflammatory immunity. In this review, we describe our current understanding of the NR activity for balancing inflammation and tolerance, the signaling cascade inducing the NR activation and functional responses, and different mechanisms of the NR-driven immune effects in the context of autoimmune diseases. We further describe the ligand-activated transcription factor the aryl hydrocarbon receptor (AhR) that exhibits analogous functionality. Moreover, we will discuss the putative role of NRs and AhR in immune regulation and disease pathogenesis providing a rationale for therapeutic targeting as a unique opportunities in the clinical management of autoimmune diseases.
核受体（NRs）是先天免疫反应和组织动态平衡的关键调节因子。有证据表明，NRs 显著影响稳态免疫调节、凋亡细胞的摄取和处理、诱导耐受以及炎症免疫的控制。在这篇综述中，我们描述了我们目前对 NR 平衡炎症和耐受的活性、诱导 NR 激活和功能反应的信号级联以及 NR 驱动的自身免疫性疾病中免疫效应的不同机制的理解。我们进一步描述了配体激活转录因子芳香烃受体（AhR），其表现出类似的功能。此外，我们将讨论 NR 和 AhR 在免疫调节和疾病发病机制中的潜在作用，为作为自身免疫性疾病临床管理中独特机会的治疗靶向提供依据。
