A novel cellular player in immune diseases

Dendritic cells (DCs) are antigen-presenting cells of the immune system that play an important role in innate and adaptive immunity. Late in the 1990s, researchers identified a subpopulation of dermal myeloid DCs with distinct phenotype, which they named 6-sulfo LacNAc+ dendritic cells (slanDCs).

SlanDCs secrete large amounts of pro-inflammatory cytokines such as TNFα and IL-12, and are implicated in the pathophysiology of numerous diseases including Crohn's disease and rheumatoid arthritis. Their undisputed role in regulating immune responses necessitates the detailed investigation of their biology. With this in mind, the EU-funded EMBRACING SLANDC project set out to study the mechanisms implicated in the maturation, migration and survival of these cells.

Scientists characterised surface marker expression on activated slanDCs and preliminarily showed that epigenetic mechanisms may regulate IL12 expression in these cells. To understand how lipopolysaccharide negatively affects slanDC survival, they looked at senescence mechanisms involving extracellular signals, autocrine/paracrine effects by endogenous cytokines and death receptor expression. Observations suggested that slanDC death could be induced, in part, through a reactive oxygen species-mediated oxidative process.

With respect to their role in disease, scientists looked at the co-localisation of slanDCs with other immune cells and investigated their migratory properties. In this context, emphasis was given to the expression of chemokine receptors and the capacity of the cells to chemoattract neutrophils.

The results obtained from this project provided new knowledge on the functional specialisation of human slanDCs. Project outcomes offer new concepts on disease pathogenesis that could help in designing novel therapies for various immune diseases.