Nature Immunology
Nature Immunology
a year ago

Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology

Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology
Giorgia Serena Gullotta, Donatella De Feo, Ekaterina Friebel, Aurora Semerano, Giulia Maria Scotti, Andrea Bergamaschi, Erica Butti, Elena Brambilla, Angela Genchi, Alessia Capotondo, Mattia Gallizioli, Simona Coviello, Marco Piccoli, Tiziana Vigo, Patrizia Della Valle, Paola Ronchi, Giancarlo Comi, Armando D’Angelo, Norma Maugeri, Luisa Roveri, Antonio Uccelli, Burkhard Becher, Gianvito Martino, Marco Bacigaluppi
Aging accounts for increased risk and dismal outcome of ischemic stroke. Here, we investigated the impact of age-related changes in the immune system on stroke. Upon experimental stroke, compared with young mice, aged mice had increased neutrophil clogging of the ischemic brain microcirculation, leading to worse no-reflow and outcomes. Aged mice showed an enhanced granulopoietic response to stroke that led to the accumulation of CD101+CD62Llo mature and CD177hiCD101loCD62Llo and CD177loCD101loCD62Lhi immature atypical neutrophils in the blood, endowed with increased oxidative stress, phagocytosis and procoagulant features. Production of CXCL3 by CD62Llo neutrophils of the aged had a key role in the development and pathogenicity of aging-associated neutrophils. Hematopoietic stem cell rejuvenation reverted aging-associated neutropoiesis and improved stroke outcome. In elderly patients with ischemic stroke, single-cell proteome profile of blood leukocytes identified CD62Llo neutrophil subsets associated with worse reperfusion and outcome. Our results unveil how stroke in aging leads to a dysregulated emergency granulopoiesis impacting neurological outcome.

Publisher URL: https://www.nature.com/articles/s41590-023-01505-1

DOI: 10.1038/s41590-023-01505-1

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.