Bell et al. report the results of the first randomized controlled phase I trial to evaluate the feasibility, safety and tolerability of intra-articular administration of autologous tolerogenic dendritic cells (DCs) in patients with inflammatory knee arthritis. CD14+ monocytes were differentiated into tolerogenic DCs and loaded with autoantigens from autologous synovial fluid; tolerogenic DC manufacture was successful for nine of the ten patients. These nine patients were divided equally into three groups that each received a different dose of tolerogenic DCs after saline irrigation of the target knee. The primary outcome of the study was met in all nine patients: none showed flare of disease in the treated knee at day 5. Adverse events considered to be potentially related to tolerogenic DC therapy were mild or moderate, and no dose–response relationship was observed. Although exploratory analyses revealed evidence suggestive of treatment efficacy in a proportion of patients, further investigation in larger cohorts is required.