Τίτλος:
Distinct transcriptional profile of blood mononuclear cells in Behçet's disease: Insights into the central role of neutrophil chemotaxis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: Both innate and adaptive immune responses are reportedly increased in Behçet's disease (BD), a chronic, relapsing systemic vasculitis lying at the intersection between autoinflammation and autoimmunity. To further study pathophysiologic molecular mechanisms operating in BD, we searched for transcriptome-wide changes in blood mononuclear cells from these patients. Methods: We performed 3' mRNA next-generation sequencing-based genome-wide transcriptional profiling followed by analysis of differential expression signatures, Kyoto Encyclopedia of Genes and Genomes pathways, GO biological processes and transcription factor signatures. Results: Differential expression analysis clustered the transcriptomes of 13 patients and one healthy subject separately from those of 10 healthy age/gender-matched controls and one patient. Among the total of 17 591 expressed protein-coding genes, 209 and 31 genes were significantly upregulated and downregulated, respectively, in BD vs controls by at least 2-fold. The most upregulated genes comprised an abundance of CC- and CXC-chemokines. Remarkably, the 5 out of top 10 upregulated biological processes involved leucocyte recruitment to peripheral tissues, especially for neutrophils. Moreover, NF-kB, TNF and IL-1 signalling pathways were prominently enhanced in BD, while transcription factor activity analysis suggested that the NF-kB p65/RELA subunit action underlies the observed differences in the BD transcriptome. Conclusion: This RNA-sequencing analysis in peripheral blood mononuclear cells derived from patients with BD does not support a major pathogenetic role for adaptive immunity-driven mechanisms, but clearly points to the action of aberrant innate immune responses with a central role played by upregulated neutrophil chemotaxis. © 2021 The Author(s) 2021.
Συγγραφείς:
Verrou, K.-M.
Vlachogiannis, N.I.
Ampatziadis-Michailidis, G.
Moulos, P.
Pavlopoulos, G.A.
Hatzis, P.
Kollias, G.
Sfikakis, P.P.
Περιοδικό:
Rheumatology (United Kingdom)
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
alpha chemokine; immunoglobulin enhancer binding protein; messenger RNA; transcription factor RelA; transcription factor; transcriptome, adult; Article; Behcet disease; clinical article; controlled study; differential expression analysis; down regulation; female; gene expression; genetic profile; genetic transcription; genome analysis; high throughput sequencing; human; human cell; IL 1 signaling; KEGG; leukocyte; male; neutrophil chemotaxis; NF kB signaling; pathophysiology; peripheral blood mononuclear cell; protein fingerprinting; TNF signaling; transcriptome sequencing; upregulation; Behcet disease; case control study; gene expression regulation; immunology; metabolism; middle aged; mononuclear cell; neutrophil; pathology, Adult; Behcet Syndrome; Case-Control Studies; Chemotaxis, Leukocyte; Female; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Neutrophils; Transcription Factors; Transcriptome
DOI:
10.1093/rheumatology/keab052
