UC San Diego

Recently studies have shown that in subjects with acute Kawasaki disease (KD), an acute pediatric vasculitis of the coronary artery, there exists a population of myeloid dendritic cells (mDCs) that have the ability to secrete the suppressive cytokine interleukin (IL)-10. Enumeration of the mDC and the regulatory T cell (Treg) populations from 3 cohorts of pediatric subjects: acute KD, acute pediatric febrile controls, and healthy children have been analyzed with an expanded panel of surface markers. From these cohorts of subjects, it was found that a newly described population of tolerogenic mDC is present in circulation and is defined as being CD11c+CD11b+CD14+ILT-4+CD4+ and by the expression of differential amounts of HLA-G. This newly described population of mDCs express the DCs maturation marker CD86, which is a T cell co-receptor. An in vitro assay plating with these newly found tolerogenic mDC population produced IL-10 in a dose dependent fashion when stimulated with scalar doses of purified fragments of the heavy chain constant region of immunoglobulin (Fc). These tolerogenic mDC did not exhibit properties that enable them to polarize T cells into peripherally induced regulatory T cells (iTreg), but the Fc stimulated tolerogenic mDC demonstrated the ability to suppress T helper 1 (Th1) differentiation as demonstrated by reduced levels of interferon (IFN)γ mRNA transcript in naïve T cell co-culture in vitro. In pediatric subjects these mDC express the adenosine 2A receptor (A2AR) which induces intracellular cAMP production, which in turn can cause production of IL-10 in these tolerogenic cells. Expression of CD31 on these tolerogenic mDC can offer a possibility for these cells to directly suppress inflamed tissue by being able to bind to CD38 on the inflamed endothelial cells.

This study identifies a new population of tolerogenic mDC in pediatrics who appears to compensate for the lack of a fully developed adaptive immune system in these young children.