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Upregulation of Interferon-inducible and damage response pathways in chronic graft-versus-host disease

ABSTRACT: To identify systemic cytokine patterns in Chronic Graft-versus-Host-Disease (CGVHD), we profiled the gene expression of circulating monocytes. Pathway analysis identified two gene sets that were significantly upregulated across a broad range of patients with inflammatory and sclerotic presentations: (1) genes induced by Type I and Type II IFN, and (2) receptor genes for innate immune responses to cellular damage. Multiple IFN-inducible genes involved in signal transduction, anti-viral function, lymphocyte homeostasis, trafficking, and antigen presentation were increased. Furthermore, upregulation of TLR/NLR/CLR receptor genes for nucleic acids, ribonucleoproteins and annexin implicated response to damaged cells as a source of activation of inflammasomes and induction of Type I IFN. Serial time courses substantiated a pattern of upregulation of multiple IFN-inducible genes at CGVHD onset, and of decline upon therapy and resolution. Corticosteroid effects could be discriminated from CGVHD gene profiles by assessment of glucocorticoid-inducible genes. Elevated expression of IFN-inducible proteins in plasma and tissue substantiated a role for IFN in lymphocyte trafficking and, through upregulation of BAFF, an involvement of IFN in B cell activation in CGVHD. These results support a unifying hypothesis of induction of IFN by innate response to cellular damage as a mechanism for initiation and persistence of CGVHD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60674 | GEO | 2017/01/04

SECONDARY ACCESSION(S): PRJNA259225

REPOSITORIES: GEO

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