Brain-derived programmed death-ligand 1 mediates immunosuppression post intracerebral hemorrhage. Issue 11 (November 2022)

• Record Type: Journal Article
• Authors: Cheng, Nuo; Wang, Hong; Zou, Ming; Jin, Wei-Na; Shi, Fu-Dong; Shi, Kaibin
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 42:Issue 11(2022)
• Page Start: 2048
• Page End: 2057
• Publication Date: 2022-11
• Subjects: Intracerebral hemorrhage -- infection -- programmed death-ligand 1 -- programed death-1 -- post-stroke immunosuppression; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X221116048
• Languages: English
• ISSNs: 0271-678X

Abstract

Immunosuppression commonly occurs after a stroke, which is believed to be associated with the increased risk of infectious comorbidities of stroke patients, while the mechanisms underlying post-stroke immunosuppression is yet to be elucidated. In the brains of intracerebral hemorrhage (ICH) patients and murine ICH models, we identified that neuron-derived programmed death-ligand 1 (PD-L1) is reduced in the perihematomal area, associating increased soluble PD-L1 level in the peripheral blood. ICH induced a significant decrease of T and natural killer (NK) cell numbers in the periphery with an upregulation of programed death-1 (PD-1) in these cells. Blocking PD-1 pathway with an anti-PD1 monoclonal antibody prevented the T and NK cell compartment contraction and spleen atrophy post-ICH, with reduced pulmonary bacterial burden and improved neurological outcome. Thus, we here identified that brain-derived PD-L1 as a new mechanism driving post-stroke immunosuppression, and anti-PD1 treatment could be potentially developed to reducing the risk of post-stroke infections.