Vicanolo Tommaso, Özcan Alaz, Li Jackson LiangYao, Huerta-López Carla, Ballesteros Iván, Rubio-Ponce Andrea, Dumitru Andra C, Nicolás-Ávila Jose Ángel, Molina-Moreno Miguel, Reyes-Gutierrez Pablo, Johnston Andrew D, Martone Catherine, Greto Eric, Quílez-Alvarez Antonio, Calvo Enrique, Bonzon-Kulichenko Elena, Álvarez-Velez Rebeca, Chooi Ming Yao, Kwok Immanuel, González-Bermúdez Blanca, Malleret Benoit, Espinosa Francisco M, Zhang Ming, Wang Yu-Long, Sun Dasheng, Zhen Chong Shu, El-Armouche Ali, Kim Kevin K, Udalova Irina A, Greco Valentina, Garcia Ricardo, Vázquez Jesús, Dopazo Ana, Plaza Gustavo R, Alegre-Cebollada Jorge, Uderhardt Stefan, Ng Lai Guan, Hidalgo Andrés
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Nature. 2025 May;641(8063):740-748. doi: 10.1038/s41586-025-08741-5. Epub 2025 Mar 19.
Defence from environmental threats is provided by physical barriers that confer mechanical protection and prevent the entry of microorganisms. If microorganisms overcome those barriers, however, innate immune cells use toxic chemicals to kill the invading cells. Here we examine immune diversity across tissues and identify a population of neutrophils in the skin that expresses a broad repertoire of proteins and enzymes needed to build the extracellular matrix. In the naive skin, these matrix-producing neutrophils contribute to the composition and structure of the extracellular matrix, reinforce its mechanical properties and promote barrier function. After injury, these neutrophils build 'rings' of matrix around wounds, which shield against foreign molecules and bacteria. This structural program relies on TGFβ signalling; disabling the TGFβ receptor in neutrophils impaired ring formation around wounds and facilitated bacterial invasion. We infer that the innate immune system has evolved diverse strategies for defence, including one that physically shields the host from the outside world.
物理屏障提供了对环境威胁的防御,这些屏障赋予机械保护并防止微生物进入。然而,如果微生物克服了这些屏障,先天免疫细胞会使用有毒化学物质杀死入侵细胞。在这里,我们研究了不同组织中的免疫多样性,并在皮肤中鉴定出一群中性粒细胞,它们表达构建细胞外基质所需的多种蛋白质和酶。在未受损伤的皮肤中,这些产生基质的中性粒细胞有助于细胞外基质的组成和结构,增强其机械性能并促进屏障功能。受伤后,这些中性粒细胞在伤口周围形成基质“环”,以抵御外来分子和细菌。这种结构程序依赖于TGFβ信号传导;使中性粒细胞中的TGFβ受体失活会损害伤口周围的环形成并促进细菌入侵。我们推断,先天免疫系统已经进化出多种防御策略,包括一种从物理上保护宿主免受外界侵害的策略。