Dendritic cell (DC) phenotypes determine the tolerogenic or pro-inflammatory outcome of an immune response. A study published in Immunity “sought to explore the role of synovial DC subsets in shaping tissue niches and regulating immune tolerance versus autoimmunity in rheumatoid arthritis (RA),” as Mariola Kurowska-Stolarska, co-corresponding author, explains. “This huge piece of work leverages multiple technologies to detail the subtypes of synovial DCs in health and active RA, their differentiation pathways from blood and their interactions with CD4+ T cells, giving new insight into the development of synovial niches in active RA as well as into how remission is initiated or lost,” notes Ranjeny Thomas, researcher of DC biology in RA who was not involved in the study.

The most dominant DC subset in the healthy synovium, located primarily beneath the macrophage-populated lining layer, was a DC2 population that expressed the immune checkpoint AXL and genes implicated in tolerance or tissue homeostasis. AXL+ DC2s appeared to develop from blood-derived KLF4+ DC2s via a KLF4+ATF3+ intermediate.