Altered innate functions of myeloid dendritic cells in ANCA-associated vasculitis

Abstract

Background Dendritic cells (DC) are critical effectors of innate and adaptive immunity, acting both as sentinels that detect the presence of pathogens and as key antigen-presenting cells that regulate the adaptive immune response. Therefore, DC play a crucial role in the control of autoimmune responses. We previously showed that blood DC numbers were strongly reduced in ANCA-associated vasculitis (AAV) likely due to their recruitment in tissues. Here, we assessed the ex vivo responsiveness of blood DC from AAV-patients to Toll-like receptors (TLRs) stimulation. Materials and methods Blood samples from 10 untreated patients with AAV during flares and before any immunosuppressive treatment (AP) were analyzed, along with 9 AAV patients in remission (RP) and 11 age-matched healthy controls (HC). Intracellular cytokine (IL-12, TNF-a ,I FN-a) production by blood DC was assessed by 8-colors flow cytometry after stimulation by Toll-like receptors of whole blood samples. Results We found that myeloid DC (mDC) from patients in acute phase exhibited a decreased IL-12 production after TLR3, 4 and 7/8 stimulation compared to patients in remission and healthy controls. These mDC also produced less TNF-a after TLR3 stimulation. Moreover, we observed a reduction in the frequency TNFa-producing plasmacytoid DC (pDC) upon TLR7/8 triggering in AP patients compared to RP patients and HC. Conclusion