Matrix-producing neutrophils populate and shield the skin

Tommaso Vicanolo, Alaz Özcan, Jackson LiangYao Li, Carla Huerta-López, Iván Ballesteros, Andrea Rubio-Ponce, Andra C. Dumitru, Jose Ángel Nicolás-Ávila, Miguel Molina-Moreno, Pablo Reyes-Gutierrez, Andrew D. Johnston, Catherine Martone, Eric Greto, Antonio Quílez-Alvarez, Enrique Calvo, Elena Bonzon-Kulichenko, Rebeca Álvarez-Velez, Ming Yao Chooi, Immanuel Kwok, Blanca González-Bermúdez, Benoit Malleret, Francisco M. Espinosa, Ming Zhang, Yu-Long Wang, Dasheng Sun, Shu Zhen Chong, Ali El-Armouche, Kevin K. Kim, Irina A. Udalova, Valentina Greco, Ricardo Garcia, Jesús Vázquez, Ana Dopazo, Gustavo R. Plaza, Jorge Alegre-Cebollada, Stefan Uderhardt (), Lai Guan Ng () and Andrés Hidalgo ()
Additional contact information
Tommaso Vicanolo: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Alaz Özcan: Yale University School of Medicine
Jackson LiangYao Li: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Carla Huerta-López: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Iván Ballesteros: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Andrea Rubio-Ponce: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Andra C. Dumitru: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Jose Ángel Nicolás-Ávila: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Miguel Molina-Moreno: Yale University School of Medicine
Pablo Reyes-Gutierrez: Yale University School of Medicine
Andrew D. Johnston: Yale School of Medicine
Catherine Martone: Yale University School of Medicine
Eric Greto: Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Antonio Quílez-Alvarez: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Enrique Calvo: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Elena Bonzon-Kulichenko: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Rebeca Álvarez-Velez: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ming Yao Chooi: Technology and Research (A*STAR)
Immanuel Kwok: Technology and Research (A*STAR)
Blanca González-Bermúdez: Universidad Politécnica de Madrid
Benoit Malleret: Technology and Research (A*STAR)
Francisco M. Espinosa: CSIC
Ming Zhang: Shanghai Jiao Tong University
Yu-Long Wang: Fudan University Shanghai Cancer Center
Dasheng Sun: Shanghai Jiao Tong University
Shu Zhen Chong: Technology and Research (A*STAR)
Ali El-Armouche: Technische Universität Dresden
Kevin K. Kim: University of Michigan
Irina A. Udalova: University of Oxford
Valentina Greco: Yale University School of Medicine
Ricardo Garcia: CSIC
Jesús Vázquez: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Ana Dopazo: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Gustavo R. Plaza: CSIC
Jorge Alegre-Cebollada: Centro Nacional de Investigaciones Cardiovasculares Carlos III
Stefan Uderhardt: Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Lai Guan Ng: Shanghai Jiao Tong University
Andrés Hidalgo: Centro Nacional de Investigaciones Cardiovasculares Carlos III

Nature, 2025, vol. 641, issue 8063, 740-748

Abstract: Abstract Defence from environmental threats is provided by physical barriers that confer mechanical protection and prevent the entry of microorganisms1. If microorganisms overcome those barriers, however, innate immune cells use toxic chemicals to kill the invading cells2,3. 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.

Date: 2025
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DOI: 10.1038/s41586-025-08741-5

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