Known for nearly a century but through mechanisms that remain elusive, cells retain a memory of inflammation that equips them to react quickly and broadly to diverse secondary stimuli. Using murine epidermal stem cells as a model, we elucidate how cells establish, maintain, and recall inflammatory memory. Specifically, we landscape and functionally interrogate temporal, dynamic changes to chromatin accessibility, histone modifications, and transcription factor binding that occur during inflammation, post-resolution, and in memory recall following injury. We unearth an essential, unifying role for the general stress-responsive transcription factor FOS, which partners with JUN and cooperates with stimulus-specific STAT3 to establish memory; JUN then remains with other homeostatic factors on memory domains, facilitating rapid FOS re-recruitment and gene re-activation upon diverse secondary challenges. Extending our findings, we offer a comprehensive, potentially universal mechanism behind inflammatory memory and less discriminate recall phenomena with profound implications for tissue fitness in health and disease.

细胞已为人所知近一个世纪，但通过仍然难以捉摸的机制，保留了炎症记忆，使它们能够对各种二次刺激做出快速而广泛的反应。我们以小鼠表皮干细胞为模型，阐明了细胞如何建立、维持和唤起炎症记忆。具体来说，我们对染色质可及性、组蛋白修饰和转录因子结合的时间动态变化进行了景观和功能性调查，这些变化发生在炎症、消退后和受伤后的记忆回忆中。我们发现了一般应激反应转录因子 FOS 的重要统一作用，它与 JUN 合作并与刺激特异性 STAT3 合作建立记忆；然后 JUN 与记忆域上的其他稳态因素保持一致，在各种次要挑战下促进快速的 FOS 重新招募和基因重新激活。扩展我们的发现，我们提供了一个全面的、潜在的普遍机制，支持炎症记忆和较少歧视的回忆现象，对健康和疾病中的组织适应性具有深远的影响。