THU0048 Pro-inflammatory il-17a-producing ccr6+ t helper memory cells change into anti-inflammatory cells with regulatory capacity upon exposure to active vitamin d. (12th June 2018)

• Record Type: Journal Article
• Authors: Dankers, W.; Davelaar, N.; van Hamburg, J.P.; van de Peppel, J.; Colin, E.M.; Lubberts, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 249
• Page End: 250
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.6997
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: In autoimmune diseases such as rheumatoid arthritis (RA), an important therapeutic goal is to normalise the imbalance between pro- and anti-inflammatory cells. In RA, especially pro-inflammatory CCR6 +T helper (Th) memory cells, characterised by IL-17A production and RORC expression, are elevated and more activated compared to healthy controls. Therefore, modulating these cells to become anti-inflammatory could contribute to restoring the immunological balance. Interestingly, the active vitamin D metabolite 1, 25(OH)2 D3 inhibits pro-inflammatory cytokine production by CCR6 +Th memory cells. Objectives: We investigated whether 1, 25(OH)2 D3 can induce an anti-inflammatory phenotype in these memory CCR6 +Th cells. Methods: CCR6 +Th memory cells, excluding Tregs, were sorted from treatment-naïve early RA patients or healthy controls and cultured with or without 1, 25(OH)2 D3 . Effects were analysed using microarray, RT-PCR, ELISA or flow cytometry. Functional properties were assessed via suppression and chemotaxis assays. Results: 1, 25(OH)2 D3 inhibits pro-inflammatory cytokines such as IL-17A, IL-17F and IL-22 in CCR6 +Th memory cells from both healthy controls and RA patients. This is accompanied by induction of anti-inflammatory factors, including IL-10 and CTLA4. Interestingly, these formerly pathogenic cells suppress proliferation of autologous CD3 +T cells, similar to classical Tregs. Importantly, the modulated memory cells still migrate towards the site of inflammation, modelled by synovial fluid, and retain their suppressive capacity in this environment. Conclusions: Committed pro-inflammatory IL-17A-producing CCR6 +Th memory cells shift towards anti-inflammatory cells with functional regulatory capacities upon exposure to active vitamin D. This process can contribute to restoring the immunological balance and inhibiting synovial inflammation in RA. Disclosure of Interest: None declared