The physiological chirality of extracellular environments is substantially affected by pathological diseases. However, how this stereochemical variation drives host immunity remains poorly understood. Here, it is reported that pathology-mimetic M-nanofibrils—but not physiology-mimetic P-nanofibrils—act as a defense mechanism that helps to restore tissue homeostasis by manipulating immunological response. Quantitative multi-omics in vivo and in vitro shows that M-nanofibrils significantly inhibit inflammation and promote tissue regeneration by upregulating M2 macrophage polarization and downstream immune signaling compared with P-nanofibrils. Molecular analysis and theoretical simulation demonstrate that M-chirality displays higher stereo-affinity to cellular binding, which induces higher cellular contractile stress and activates mechanosensitive ion channel PIEZOl to conduct Ca²⁺ influx. In turn, the nuclear transfer of STAT is biased by Ca²⁺ influx to promote M2 polarization. These findings underscore the structural mechanisms of disease, providing design basis for immunotherapy with bionic functional materials.

中文翻译：

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通过操纵免疫反应实现手性偏向组织稳态

细胞外环境的生理手性很大程度上受病理疾病的影响。然而，这种立体化学变化如何驱动宿主免疫仍然知之甚少。在这里，据报道，模拟病理学的 M-纳米原纤维 - 但不是模拟生理学的 P-纳米原纤维 - 作为一种防御机制，通过操纵免疫反应帮助恢复组织稳态。体内和体外的定量多组学研究表明，与 P-纳米原纤维相比，M-纳米原纤维通过上调 M2 巨噬细胞极化和下游免疫信号传导显着抑制炎症并促进组织再生。分子分析和理论模拟表明，M-手性对细胞结合表现出更高的立体亲和力，²⁺涌入。反过来，STAT的核转移被Ca ²⁺流入偏向以促进M2极化。这些发现强调了疾病的结构机制，为使用仿生功能材料进行免疫治疗提供了设计基础。