Cargando…
MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis
BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191918/ https://www.ncbi.nlm.nih.gov/pubmed/30332984 http://dx.doi.org/10.1186/s10020-018-0056-z |
_version_ | 1783363807282724864 |
---|---|
author | Möhnle, P Hirschberger, S Hinske, L C Briegel, J Hübner, M Weis, S Dimopoulos, G Bauer, M Giamarellos-Bourboulis, E J Kreth, S |
author_facet | Möhnle, P Hirschberger, S Hinske, L C Briegel, J Hübner, M Weis, S Dimopoulos, G Bauer, M Giamarellos-Bourboulis, E J Kreth, S |
author_sort | Möhnle, P |
collection | PubMed |
description | BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). RESULTS: T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-β. The individual extent of immunosuppression differed markedly. MicroRNA-143, − 150 and − 223 independently indicated T-cell immunoparalysis and significantly correlated with patient’s IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 – both predominantly expressed in T-cells – retained strong power of discrimination also in whole blood samples. CONCLUSIONS: These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0056-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6191918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61919182018-10-31 MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis Möhnle, P Hirschberger, S Hinske, L C Briegel, J Hübner, M Weis, S Dimopoulos, G Bauer, M Giamarellos-Bourboulis, E J Kreth, S Mol Med Research Article BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). RESULTS: T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-β. The individual extent of immunosuppression differed markedly. MicroRNA-143, − 150 and − 223 independently indicated T-cell immunoparalysis and significantly correlated with patient’s IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 – both predominantly expressed in T-cells – retained strong power of discrimination also in whole blood samples. CONCLUSIONS: These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s10020-018-0056-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-17 /pmc/articles/PMC6191918/ /pubmed/30332984 http://dx.doi.org/10.1186/s10020-018-0056-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Möhnle, P Hirschberger, S Hinske, L C Briegel, J Hübner, M Weis, S Dimopoulos, G Bauer, M Giamarellos-Bourboulis, E J Kreth, S MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title | MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_full | MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_fullStr | MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_full_unstemmed | MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_short | MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis |
title_sort | micrornas 143 and 150 in whole blood enable detection of t-cell immunoparalysis in sepsis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191918/ https://www.ncbi.nlm.nih.gov/pubmed/30332984 http://dx.doi.org/10.1186/s10020-018-0056-z |
work_keys_str_mv | AT mohnlep micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT hirschbergers micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT hinskelc micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT briegelj micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT hubnerm micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT weiss micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT dimopoulosg micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT bauerm micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT giamarellosbourboulisej micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis AT kreths micrornas143and150inwholebloodenabledetectionoftcellimmunoparalysisinsepsis |