O024 Human memory TH17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active vitamin D

Introduction In autoimmune diseases such as rheumatoid arthritis (RA), an important therapeutic goal is to normalise the imbalance between pro- and anti-inflammatory cells. This imbalance is illustrated by elevated levels and activity of memory CCR6 +Th17 cell populations, such as Th17 and Th17.1 cells, in RA patients compared to healthy controls. Therefore, modulating these cells to become anti-inflammatory could contribute to restoring the immunological balance. Objectives The active vitamin D metabolite 1,25(OH) 2 D 3 is known to inhibit pro-inflammatory cytokine production by CCR6 +Th memory cells. Therefore, we investigated whether 1,25(OH) 2 D 3 can induce an anti-inflammatory phenotype in these memory T cells. Methods CCR6 +Th memory cells, excluding Tregs, were sorted from treatment-naive early RA patients or healthy controls and cultured with or without 1,25(OH) 2 D 3 . 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 D 3 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 can become 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