Glucocorticoids Regulate Bone Marrow B Lymphopoiesis After Stroke.
Circ Res
; 124(9): 1372-1385, 2019 04 26.
Article
en En
| MEDLINE
| ID: mdl-30782088
ABSTRACT
RATIONALE After a stroke, patients frequently experience altered systemic immunity resulting in peripheral immunosuppression and higher susceptibility to infections, which is at least partly attributed to lymphopenia. The mechanisms that profoundly change the systemic leukocyte repertoire after stroke are incompletely understood. Emerging evidence indicates that stroke alters hematopoietic output of the bone marrow. OBJECTIVE:
To explore the mechanisms that lead to defects of B lymphopoiesis after ischemic stroke. METHODS ANDRESULTS:
We here report that ischemic stroke triggers brain-bone marrow communication via hormonal long-range signals that regulate hematopoietic B lineage decisions. Bone marrow fluorescence-activated cell sorter analyses and serial intravital microscopy indicate that transient middle cerebral artery occlusion in mice arrests B-cell development beginning at the pro-B-cell stage. This phenotype was not rescued in Myd88-/- and TLR4-/- mice with disrupted TLR (Toll-like receptor) signaling or after blockage of peripheral sympathetic nerves. Mechanistically, we identified stroke-induced glucocorticoid release as the main instigator of B lymphopoiesis defects. B-cell lineage-specific deletion of the GR (glucocorticoid receptor) in CD19-Cre loxP Nr3c1 mice attenuated lymphocytopenia after transient middle cerebral artery. In 20 patients with acute stroke, increased cortisol levels inversely correlated with blood lymphocyte numbers.CONCLUSIONS:
Our data demonstrate that the hypothalamic-pituitary-adrenal axis mediates B lymphopoiesis defects after ischemic stroke.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células de la Médula Ósea
/
Linfocitos B
/
Receptores de Glucocorticoides
/
Corticoesteroides
/
Accidente Cerebrovascular
/
Linfopoyesis
Límite:
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Circ Res
Año:
2019
Tipo del documento:
Article