Increased CD1c+ mDC1 with mature phenotype regulated by TNFα–p38 MAPK in autoimmune ocular inflammatory disease

Abstract

In this study we investigated the role of blood CD1c+ myeloid dendritic cells 1 (mDC1), a key mDC subtype, in patients with autoimmune uveitis. We observed a significant increase of blood CD1c+ mDC1 in uveitis patients. The increased CD1c+ mDC1 exhibited high HLADR expression and less antigen uptake. CD1c+ mDC1 were divided into two subpopulations. CD1chi mDC1 subpopulation showed less antigen uptake and higher HLADR expression compared to CD1clo mDC1 subpopulation. Importantly, the CD1chi mDC1 subpopulation was increased in uveitis patients. In vitro, mature monocyte-derived dendritic cells (MoDCs), characterized by lower levels of antigen uptake, induced more CD4+CD62L- T helper cell proliferation. The mature phenotype and function of CD1c+ mDC1 were regulated by TNFα via a p38 MAPK-dependent pathway. These data show that alterations in the systemic immune response are involved in the pathogenesis of autoimmune uveitis and invite the therapeutic possibility of attenuating uveitis by manipulating blood CD1c+ mDC1.