Department of Pathology, New York University Langone Health, New York, NY, USA.
Department of Medicine, New York University Langone Health, New York, NY, USA.
Nature. 2022 Jul;607(7918):249-255. doi: 10.1038/s41586-022-04919-3. Epub 2022 Jul 13.
Our body has a remarkable ability to remember its past encounters with allergens, pathogens, wounds and irritants, and to react more quickly to the next experience. This accentuated sensitivity also helps us to cope with new threats. Despite maintaining a state of readiness and broadened resistance to subsequent pathogens, memories can also be maladaptive, leading to chronic inflammatory disorders and cancers. With the ever-increasing emergence of new pathogens, allergens and pollutants in our world, the urgency to unravel the molecular underpinnings of these phenomena has risen to new heights. Here we reflect on how the field of inflammatory memory has evolved, since 2007, when researchers realized that non-specific memory is contained in the nucleus and propagated at the epigenetic level. We review the flurry of recent discoveries revealing that memory is not just a privilege of the immune system but also extends to epithelia of the skin, lung, intestine and pancreas, and to neurons. Although still unfolding, epigenetic memories of inflammation have now been linked to possible brain disorders such as Alzheimer disease, and to an elevated risk of cancer. In this Review, we consider the consequences-good and bad-of these epigenetic memories and their implications for human health and disease.
我们的身体具有卓越的能力,能够记住过去与过敏原、病原体、伤口和刺激物的接触,并在下一次接触时更快地做出反应。这种增强的敏感性还有助于我们应对新的威胁。尽管保持着准备状态和对后续病原体的广泛抵抗力,但记忆也可能不适应,导致慢性炎症性疾病和癌症。随着我们世界中新出现的病原体、过敏原和污染物的不断增加,揭示这些现象的分子基础的紧迫性已经达到了新的高度。在这里,我们回顾了炎症记忆领域自 2007 年以来的发展,当时研究人员意识到非特异性记忆包含在细胞核中,并在表观遗传水平上传播。我们回顾了最近大量发现揭示的记忆不仅是免疫系统的特权,还扩展到皮肤、肺、肠道和胰腺的上皮细胞以及神经元。尽管仍在展开,但炎症的表观遗传记忆现在已经与阿尔茨海默病等可能的大脑疾病以及癌症风险增加联系在一起。在这篇综述中,我们考虑了这些表观遗传记忆的好坏后果及其对人类健康和疾病的影响。