Co-option of Neutrophil Fates by Tissue Environments

Iván Ballesteros, Andrea Rubio-Ponce, Marco Genua, Eleonora Lusito, Immanuel Kwok, Gabriel Fernández-Calvo, Tariq E. Khoyratty, Erinke van Grinsven, Sara González-Hernández, José Ángel Nicolás-Ávila, Tommaso Vicanolo, Antonio Maccataio, Alberto Benguría, Jackson Liang Yao Li, José M. Adrover, Alejandra Aroca-Crevillen, Juan A. Quintana, Sandra Martín-Salamanca, Francisco Mayo, Stefanie AscherGiulia Barbiera, Oliver Soehnlein, Matthias Gunzer, Florent Ginhoux, Fátima Sánchez-Cabo, Estanislao Nistal-Villán, Christian Schulz, Ana Dopazo, Christoph Reinhardt, Irina A. Udalova, Lai Guan Ng, Renato Ostuni, Andrés Hidalgo

Research output: Contribution to journalArticlepeer-review

Abstract

Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer, yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model to track neutrophil fates, we found short but variable lifetimes across multiple tissues. Through analysis of the receptor, transcriptional, and chromatin accessibility landscapes, we identify varying neutrophil states and assign non-canonical functions, including vascular repair and hematopoietic homeostasis. Accordingly, depletion of neutrophils compromised angiogenesis during early age, genotoxic injury, and viral infection, and impaired hematopoietic recovery after irradiation. Neutrophils acquired these properties in target tissues, a process that, in the lungs, occurred in CXCL12-rich areas and relied on CXCR4. Our results reveal that tissues co-opt neutrophils en route for elimination to induce programs that support their physiological demands. Neutrophils demonstrate plasticity in form and function depending upon the tissue types.

Original languageEnglish
Pages (from-to)1282-1297.e18
JournalCell
Volume183
Issue number5
DOIs
Publication statusPublished - Nov 25 2020

Keywords

  • angiogenesis
  • immune heterogeneity
  • immune niche
  • innate immunity
  • neutrophil lifespan
  • neutrophils
  • single-cell analysis
  • tissue-resident cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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