Myeloid dendritic cells with elevated CD1c expression in non-infectious uveitis patients exhibited mature phenotype through the regulation of TNFa-p38 MAPK pathway (HUM1P.273)

Abstract

Abstract Our longitudinal data has shown that the level of CD1c+ myeloid dendritic cells 1 (mDC1) from peripheral blood reflects disease activity in autoimmune non-infectious uveitis patients. However, the role of CD1c+ mDC1 is not clear in autoimmune uveitis patients. Here, we demonstrate that the mDC1 in patients with non-infectious uveitis (n=74) was increased compared to age and gender-matched healthy controls (n=96). The increased CD1c+ mDC1 exhibited high HLADR expression and less antigen uptake. CD1c+ mDC1 were further divided into two subpopulations based on the level of CD1c expression. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi mDC1 subpopulation was significantly increased in uveitis patients. By utilizing monocyte-derived dendritic cells (MoDCs) for in vitro studies, MoDCs with less antigen uptake and higher levels of CD1c induced more CD4+ T helper cell activation and proliferation. TNFa, increased in uveitis patient sera, reduced the antigen uptake in a dose-dependent manner and increased the phosphorylated p38 expression on MoDCs. A p38 inhibitor significantly inhibited the expression of CD1c during dendritic cell differentiation from monocytes. In conclusion, CD1c is a maturation marker of mDC1, increased in uveitis patients and correlated with disease activity. The high CD1c expression and low antigen uptake are mediated by the TNFa-activated p38 MAPK pathway.