Pediatric tolerogenic DCs expressing CD4 and immunoglobulin-like transcript receptor (ILT)-4 secrete IL-10 in...

We characterized a novel population of tolerogenic myeloid dendritic cells (tmDCs) defined as CD11c⁺ CD11b⁺ CD14⁺ CD4⁺ and immunoglobulin-like transcript receptor (ILT)-4⁺ that are significantly more abundant in the circulation of infants and young children than in adults. TmDCs secrete the immunosuppressive lymphokine interleukin (IL)-10 when stimulated with the heavy constant region of immunoglobulins (Fc) and express high levels of the adenosine A_2A receptor (A_2A R), which, when activated by adenosine, inhibits the release of pro-inflammatory cytokines from most immune cells. Here we show that stimulation of the A_2A R on tmDCs by regadenoson or N-ethylcarboxamidoadenosine (NECA) rapidly increases cyclic AMP accumulation and enhances IL-10 production under Fc stimulatory conditions. In co-culture experiments, tmDCs inhibit the differentiation of naïve T cells to a pro-inflammatory phenotype. In conclusion, although DCs are classically viewed as antigen presenting cells that activate T cells, we show an independent role of tmDCs in pediatric immune regulation that may be important for suppressing T cell responses to neoantigens in infants and young children.