Pediatric tolerogenic DCs expressing CD4 and immunoglobulin‐like transcript receptor (ILT)‐4 secrete IL‐10 in response to Fc and adenosine

A Franco, J Kumar, G Lin, N Behnamfar… - European journal of …, 2018 - Wiley Online Library
A Franco, J Kumar, G Lin, N Behnamfar, LE Hsieh, C Shimizu, AH Tremoulet, JC Burns…
European journal of immunology, 2018Wiley Online Library
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 A2A receptor (A2AR), which, when activated by adenosine, inhibits the …
Abstract
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 A2A receptor (A2AR), which, when activated by adenosine, inhibits the release of pro‐inflammatory cytokines from most immune cells. Here we show that stimulation of the A2AR 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.
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