IL-6 Mediated Transcriptional Programming of Naive CD4+ T Cells in Early Rheumatoid Arthritis Drives Dysregulated Effector Function.

ABSTRACT: Objective: We have previously shown that increased circulating interleukin-6 (IL-6) results in enhanced CD4+ T cell signaling via signal transduction and activator of transcription-3 (STAT3) in early rheumatoid arthritis (RA). We tested the hypothesis that transcriptional "imprinting" of T-cells by this mechanism skews downstream effector responses, reinforcing immune dysregulation at a critical, but targetable, disease phase. Methods: We modeled naïve CD4+ T cell exposure to pathophysiological concentrations of IL-6 in vitro, assessing the dynamic transcriptional and functional consequences for downstream effector cells utilizing microarray and flow cytometry. Fresh blood from treatment-naïve early arthritis patients was phenotyped in parallel for comparison. Resul

SUBMITTER: Ridgley LA 

PROVIDER: S-EPMC6618050 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature