Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells
Dan Hu, Emily Tjon, Karin Andersson, Gabriela M. Molica, Minh Pham, Brian C. Healy, Gopal Murugaiyan, Nathalie Pochet, Vijay K. Kuchroo, Maria Bokarewa, Howard L. Weiner
Abstract
Significance Identifying signaling pathways contributing to resistance to anti-TNF therapy in rheumatoid arthritis is crucial for the development of new therapeutic strategies for refractory rheumatoid arthritis. Th17 cells, a subset of proinflammatory CD4 + T cells, are implicated in the pathogenesis of the disease. We analyzed the gene expression profiles of Th17-enriched CD4 + T cells in anti-TNF–treated patients with rheumatoid arthritis and found that the elevated expression levels of transcription factor USF2 in anti-TNF refractory patients were associated with increased proinflammatory signaling of Th17 cells. USF2-knockdown experiments in Th17 cells revealed that USF2 promotes the pathogenicity of Th17 cells. These findings have implications for the development of new therapeutic strategies for refractory rheumatoid arthritis.