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.Bacigaluppi and colleagues report that the accumulation of atypical mature and immature neutrophil subsets and a dysregulated emergency granulopoiesis response in aged mice and humans affect the outcome of stroke.

Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology / Gullotta, G. S.; De Feo, D.; Friebel, E.; Semerano, A.; Scotti, G. M.; Bergamaschi, A.; Butti, E.; Brambilla, E.; Genchi, A.; Capotondo, A.; Gallizioli, M.; Coviello, S.; Piccoli, M.; Vigo, T.; Della Valle, P.; Ronchi, P.; Comi, G.; D'Angelo, A.; Maugeri, N.; Roveri, L.; Uccelli, A.; Becher, B.; Martino, G.; Bacigaluppi, M.. - In: NATURE IMMUNOLOGY. - ISSN 1529-2916. - 24:6(2023), pp. 925-940. [10.1038/s41590-023-01505-1]

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

Gullotta G. S.
Primo
;
Genchi A.;Comi G.;Martino G.
Penultimo
Supervision
;
Bacigaluppi M.
2023-01-01

Abstract

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.Bacigaluppi and colleagues report that the accumulation of atypical mature and immature neutrophil subsets and a dysregulated emergency granulopoiesis response in aged mice and humans affect the outcome of stroke.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/159579
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