Sep 5, 2019

Molecular Characterization of Human Lymph Node Stromal Cells During the Earliest Phases of Rheumatoid Arthritis

Frontiers in Immunology
Emmanuel KarouzakisL G M van Baarsen

Abstract

Rheumatoid arthritis (RA) is a progressive, destructive autoimmune arthritis. Break of tolerance and formation of autoantibodies occur years before arthritis. Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) play a crucial role in shaping the immune response and maintaining peripheral tolerance. Here we performed the first epigenomic characterization of LNSCs during health and early RA, by analyzing their transcriptome and DNA methylome in LNSCs isolated from lymph node needle biopsies obtained from healthy controls (HC), autoantibody positive RA-risk individuals and patients with established RA. Of interest, LNSCs from RA-risk individuals and RA patients revealed a common significantly differential expressed gene signature compared with HC LNSCs. Pathway analysis of this common signature showed, among others, significant enrichment of pathways affecting the extracellular matrix (ECM), cholesterol biosynthesis and immune system. In a gel contraction assay LNSCs from RA-risk individuals and RA patients showed impaired collagen contraction compared to healthy LNSCs. In RA LNSCs a significant enrichment was observed for genes involved in cytokine signaling, hemostasis and packaging of telome...Continue Reading

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Mentioned in this Paper

Immune Response
Autoantibodies
Genes
Extracellular Matrix Constituent Secretion
Cholesterol Biosynthetic Process
AMBP gene
Extracellular Matrix
Biopsy or Excision of Lymph Node(S); by Needle, Superficial (Eg, Cervical, Inguinal, Axillary)
Contraction (Finding)
DNA Methylation

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