| First Author | Gullotta GS | Year | 2023 |
| Journal | Nat Immunol | Volume | 24 |
| Issue | 6 | Pages | 925-940 |
| PubMed ID | 37188941 | Mgi Jnum | J:341048 |
| Mgi Id | MGI:7495991 | Doi | 10.1038/s41590-023-01505-1 |
| Citation | Gullotta GS, et al. (2023) Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology. Nat Immunol 24(6):925-940 |
| abstractText | 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(+)CD62L(lo) mature and CD177(hi)CD101(lo)CD62L(lo) and CD177(lo)CD101(lo)CD62L(hi) immature atypical neutrophils in the blood, endowed with increased oxidative stress, phagocytosis and procoagulant features. Production of CXCL3 by CD62L(lo) 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 CD62L(lo) neutrophil subsets associated with worse reperfusion and outcome. Our results unveil how stroke in aging leads to a dysregulated emergency granulopoiesis impacting neurological outcome. |
