A novel role for RGMa in modulation of bone marrow-derived dendritic cells maturation induced by lipopolysaccharide

• The expression of key surface molecules were decreased in RGMa-silenced DCs with LPS treatment.
• RGMa-transfected DCs reduced levels of IL-12p70 and TNF-α, and increased level of IL-10, after LPS treatment.
• RGMa-transfected DCs had a reduced ability to induce T cell activation and differentiation, after LPS treatment.

Repulsive guidance molecule a (RGMa) is known to mediate immune responses and has been indicated to modulates T cell activation and autoimmune diseases by dendritic cells (DCs), which hints its significant function in the latter cells. The aim of our study, therefore, was to evaluate the function of RGMa in DC maturation. We found that small interfering RNA (siRNA) successfully silenced the expression of RGMa in DCs. Even after LPS stimulation, RGMa-silenced DCs displayed an immature morphology, characterized by small, round cells with a few cell processes and organelles, and many pinocytotic vesicles. In the presence of LPS, RGMa siRNA transfection markedly reduced levels of CD80, CD86, CD40, and MHC II expression, as well as the secretion of IL-12p70 and TNF-α. With LPS treatment, RGMa siRNA-transfected DCs also showed increased levels of IL-10 and endocytosis. Moreover, in the presence of LPS, RGMa siRNA-transfected DCs displayed a low ability to induce T cell proliferation and differentiation, compared with negative control (NTi)-transfected or control DCs (p < 0.05 for both). We conclude that after LPS stimulation, RGMa siRNA-transfected DCs show immunoregulatory and tolerogenic characteristics, which provides new insights into the immune system.