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Verfasst von:Siegler, Benedikt Hermann [VerfasserIn]   i
 Uhle, Florian [VerfasserIn]   i
 Lichtenstern, Christoph [VerfasserIn]   i
 Arens, Christoph [VerfasserIn]   i
 Bartkuhn, Marek [VerfasserIn]   i
 Weigand, Markus A. [VerfasserIn]   i
 Weiterer, Sebastian [VerfasserIn]   i
Titel:Impact of human sepsis on CCCTC-binding factor associated monocyte transcriptional response of Major Histocompatibility Complex II components
Verf.angabe:Benedikt Hermann Siegler, Florian Uhle, Christoph Lichtenstern, Christoph Arens, Marek Bartkuhn, Markus Alexander Weigand, Sebastian Weiterer
E-Jahr:2018
Jahr:September 13, 2018
Umfang:14 S.
Fussnoten:Gesehen am 28.09.2018
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2018
Band/Heft Quelle:13(2018), 9, Artikel-ID e0204168
ISSN Quelle:1932-6203
Abstract:Background Antigen presentation on monocyte surface to T-cells by Major Histocompatibility Complex, Class II (MHC-II) molecules is fundamental for pathogen recognition and efficient host response. Accordingly, loss of Major Histocompatibility Complex, Class II, DR (HLA-DR) surface expression indicates impaired monocyte functionality in patients suffering from sepsis-induced immunosuppression. Besides the impact of Class II Major Histocompatibility Complex Transactivator (CIITA) on MHC-II gene expression, X box-like (XL) sequences have been proposed as further regulatory elements. These elements are bound by the DNA-binding protein CCCTC-Binding Factor (CTCF), a superordinate modulator of gene transcription. Here, we hypothesized a differential interaction of CTCF with the MHC-II locus contributing to an altered monocyte response in immunocompromised septic patients. Methods We collected blood from six patients diagnosed with sepsis and six healthy controls. Flow cytometric analysis was used to identify sepsis-induced immune suppression, while inflammatory cytokine levels in blood were determined via ELISA. Isolation of CD14++ CD16—monocytes was followed by (i) RNA extraction for gene expression analysis and (ii) chromatin immunoprecipitation to assess the distribution of CTCF and chromatin modifications in selected MHC-II regions. Results Compared to healthy controls, CD14++ CD16—monocytes from septic patients with immune suppression displayed an increased binding of CTCF within the MHC-II locus combined with decreased transcription of CIITA gene. In detail, enhanced CTCF enrichment was detected on the intergenic sequence XL9 separating two subregions coding for MHC-II genes. Depending on the relative localisation to XL9, gene expression of both regions was differentially affected in patients with sepsis. Conclusion Our experiments demonstrate for the first time that differential CTCF binding at XL9 is accompanied by uncoupled MHC-II expression as well as transcriptional and epigenetic alterations of the MHC-II regulator CIITA in septic patients. Overall, our findings indicate a sepsis-induced enhancer blockade mediated by variation of CTCF at the intergenic sequence XL9 in altered monocytes during immunosuppression.
DOI:doi:10.1371/journal.pone.0204168
URL:kostenfrei: Volltext ; Verlag: http://dx.doi.org/10.1371/journal.pone.0204168
 kostenfrei: Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204168
 DOI: https://doi.org/10.1371/journal.pone.0204168
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Chromatin
 DNA transcription
 Gene expression
 Gene regulation
 Genetic loci
 Immune suppression
 Monocytes
 Sepsis
K10plus-PPN:1581406819
Verknüpfungen:→ Zeitschrift
 
 
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