Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Adv Immunol. 2024;161:17-51. doi: 10.1016/bs.ai.2024.03.004. Epub 2024 Mar 30.
The innate immune system uses a distinct set of germline-encoded pattern recognition receptors to recognize molecular patterns initially thought to be unique to microbial invaders, named pathogen-associated molecular patterns. The concept was later further developed to include similar molecular patterns originating from host cells during tissue damage, known as damage-associated molecular patterns. However, recent advances in the mechanism of monogenic inflammatory diseases have highlighted a much more expansive repertoire of cellular functions that are monitored by innate immunity. Here, we summarize several examples in which an innate immune response is triggered when homeostasis of macromolecule in the cell is disrupted in non-infectious or sterile settings. These ever-growing sensing mechanisms expand the repertoire of innate immune recognition, positioning it not only as a key player in host defense but also as a gatekeeper of cellular homeostasis. Therapeutics inspired by these advances to restore cellular homeostasis and correct the immune system could have far-reaching implications.
先天免疫系统使用一组独特的胚系编码模式识别受体来识别最初被认为是微生物入侵所特有的分子模式，这些分子模式被命名为病原体相关分子模式。后来，这一概念进一步发展为包括来自宿主细胞在组织损伤期间产生的类似分子模式，称为损伤相关分子模式。然而，单基因炎症性疾病机制的最新进展强调了先天免疫监测的细胞功能的范围要广泛得多。在这里，我们总结了一些例子，即在非传染性或无菌环境中细胞内大分子的内环境稳定被破坏时，先天免疫反应会被触发。这些不断发展的传感机制扩大了先天免疫识别的范围，使先天免疫系统不仅成为宿主防御的关键因素，而且成为细胞内环境稳定的守门员。受这些进展启发的恢复细胞内环境稳定和纠正免疫系统的治疗方法可能具有深远的意义。
