Differential polarization and activation dynamics of systemic T helper cell subsets after aneurysmal subarachnoid hemorrhage (SAH) and during post-SAH complications

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Chaudhry , S R , Kahlert , U D , Kinfe , T M , Endl , E , Dolf , A , Niemelä , M , Haenggi , D & Muhammad , S 2021 , ' Differential polarization and activation dynamics of systemic T helper cell subsets after aneurysmal subarachnoid hemorrhage (SAH) and during post-SAH complications ' , Scientific Reports , vol. 11 , no. 1 , 14226 . https://doi.org/10.1038/s41598-021-92873-x

Titel: Differential polarization and activation dynamics of systemic T helper cell subsets after aneurysmal subarachnoid hemorrhage (SAH) and during post-SAH complications
Författare: Chaudhry, Shafqat Rasul; Kahlert, Ulf Dietrich; Kinfe, Thomas Mehari; Endl, Elmar; Dolf, Andreas; Niemelä, Mika; Haenggi, Daniel; Muhammad, Sajjad
Upphovmannens organisation: Department of Neurosciences
HUS Neurocenter
Neurokirurgian yksikkö
University of Helsinki
Clinicum
Datum: 2021-07-09
Språk: eng
Sidantal: 10
Tillhör serie: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-92873-x
Permanenta länken (URI): http://hdl.handle.net/10138/334466
Abstrakt: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Devastating post-SAH complications, such as cerebral vasospasm (CVS), delayed cerebral ischemia or seizures to mention a few, are mainly responsible for the poor clinical outcome. Inflammation plays an indispensable role during early brain injury (EBI) and delayed brain injury (DBI) phases over which these complications arise. T helper cells are the major cytokine secreting cells of adaptive immunity that can polarize to multiple functionally unique sub-populations. Here, we investigate different CD4+T cell subsets during EBI and DBI phases after SAH, and their dynamics during post-SAH complications. Peripheral venous blood from 15 SAH patients during EBI and DBI phases, was analyzed by multicolour flowcytometry. Different subsets of CD3+CD4+T cells were characterized by differential cell surface expression of CXCR3 and CCR6 into Th1, Th2, Th17, whereas Tregs were defined by CD25(hi)CD127(lo). The analysis of activation states was done by the expression of stable activation markers CD38 and HLA-DR. Interestingly, compared to healthy controls, Tregs were significantly increased during both EBI and DBI phases. Different activation states of Tregs showed differential significant increase during EBI and DBI phases compared to controls. HLA-DR-CD38+Tregs were significantly increased during DBI phase compared to EBI phase in SAH patients developing CVS, seizures and infections. However, HLA-DR-CD38-Tregs were significantly reduced during EBI phase in patients with cerebral ischemia (CI) compared to those without CI. HLA-DR-CD38-Th2 cells were significantly increased during EBI phase compared to controls. A significant reduction in Th17/Tregs and HLA-DR-CD38+Th17/Tregs ratios was observed during both EBI and DBI phases compared to controls. While HLA-DR-CD38-Th17/Tregs and HLA-DR-CD38-Th1/Th2 ratios were impaired only during EBI phase compared to controls. In conclusion, CD4+T cell subsets display dynamic and unique activation patterns after SAH and during the course of the manifestation of post-SAH complications, which may be helpful for the development of precision neurovascular care. However, to claim this, confirmatory studies with larger patient cohorts, ideally from different ethnic backgrounds, are required. Moreover, our descriptive study may be the grounds for subsequent lab endeavors to explore the underlying mechanisms of our observations.
Subject: MECHANISMS
CD4(+)
3124 Neurology and psychiatry
3126 Surgery, anesthesiology, intensive care, radiology
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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