OP0141 1, 25(OH)2D3 modulates gene expression involved in cytokine production, proliferation, survival and migration of TH17 cells from patients with rheumatoid arthritis. (23rd January 2014)

• Record Type: Journal Article
• Authors: Dankers, W.; van Hamburg, J.P.; Asmawidjaja, P.S.; Davelaar, N.; Wen, K.; Mus, A.M.C.; Colin, E.M.; van Leeuwen, J.P.T.M.; Hazes, J.M.W.; Lubberts, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 101
• Page End: 101
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.1824
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Vitamin D has suppressive effects on autoimmune diseases, such as rheumatoid arthritis (RA). Within these diseases, T-helper-17 (Th17) cells have been implicated toplay a crucial role in the development and progression of chronic inflammation. Recently, we have found that the active vitamin D compound, 1, 25(OH)2 D3, has direct suppressive effects on both human and mouse Th17 cytokine expression and activity. Objectives: Using gene-expression profiling, we aim to identify molecular targets of 1, 25(OH)2 D3 signaling underlying the suppressive action of 1, 25(OH)2 D3 in Th17 cells from patients with RA. Methods: Primary Th17 cells were sorted from peripheral blood of treatment naïve patients with early RA and cultured with or without 1, 25(OH)2 D3 . From these cultures gene-expression profiles were generated. Expression of genes of interest was confirmed by Q-PCR and/or specific ELISA. Results: In the presence of 1, 25(OH)2 D3, protein expression of Th17 associated cytokines IL-17A and IL-22 was inhibited, while in contrast the anti-inflammatory cytokine IL-10 was induced. These findings were supported by the gene-expression profiles from these cultures. Furthermore, 1, 25(OH)2 D3 inhibited transcription of the cytokine receptors IL-23R and IL-7R, which are involved in Th17 survival and proliferation. Chemokines CCL20 and CXCL10 were down-regulated and chemokine receptors CCR2, CXCR6, CXCR3 and CCR10 were up-regulated. Importantly, Rorgt, which is critically involved in Th17 differentiation and function and the cell-size regulator and oncogene, c-Myc were down-regulated by 1, 25(OH)2 D3 . Conclusions: From these findings, we concluded that 1, 25(OH)2 D3 modulates the expression of genes involved in cytokine production, proliferation, survival and migration of Th17 cells. These data indicate that 1, 25(OH)2 D3 not only suppresses Th17 cell activity but also regulates migration of these cells to sites of tissue inflammation in RA. Disclosure of Interest: None Declared