Matrix-producing neutrophils populate and shield the skin

Matrix-producing neutrophils populate and shield the skin

Nature

10.1038/s41586-025-08741-5

https://doi.org/10.1038/s41586-025-08741-5

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, Andrés Hidalgo

Cell Biology

19 March 2025

Vicanolo, T., Özcan, A., Li, J. L., Huerta-López, C., Ballesteros, I., Rubio-Ponce, A., Dumitru, A. C., Nicolás-Ávila, J. Á., Molina-Moreno, M., Reyes-Gutierrez, P., Johnston, A. D., Martone, C., Greto, E., Quílez-Alvarez, A., Calvo, E., Bonzon-Kulichenko, E., Álvarez-Velez, R., Chooi, M. Y., Kwok, I., … Hidalgo, A. (2025). Matrix-producing neutrophils populate and shield the skin. Nature, 641(8063), 740–748. https://doi.org/10.1038/s41586-025-08741-5

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.

Publisher Copyright

This research is supported by core funding from: Singapore Immunology Network
Grant Reference no. : NA

This is a post-peer-review, pre-copyedit version of an article published in Nature. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41586-025-08741-5

https://oar.a-star.edu.sg/communities-collections/articles/22903

0028-0836
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Singapore Immunology Network