Reversal of iC3b-inhibited dendritic cell differentiation via inhibition of the extracellular signal-regulated mitogen-activated protein kinase promotes CD4+ T cell proliferation

ObjectivesTo investigate the roles of ERK1/2 and p38 MAPK cascades in the differentiation of iC3b-combined CD14+ monocyte into CD1a+ MDDC, and to study how these cells influence CD4+ T cell proliferation.MethodsCD14+ monocyte was co-cultured with iC3b with or without inhibitors specific for ERK1/2 or p38 MAPK pathways for 2 days, then the expressions of CD14, CD1a, phophso-ERK1/2, phophso-p38, IL-10 and IL-12 p70 were detected, and CD4+ T cell proliferation was measured via 3H-TdR as well.ResultsMaturation of CD1a+ DC was inhibited by iC3b along with downregulated expressions of CD1a, phophso-p38 and IL-12p70 and upregulated expressions of phophso-ERK1/2 and IL-10, and the CD4+ T cell proliferation was restrained accordingly. When pretreated with inhibitor specific for ERK1/2 pathway, the inhibited maturation of imDC was reversed prominently with a higher level expression of CD1a and IL-12p70, whereas expressions of phophso-ERK1/2 and IL-10 were lowered, and accordingly the CD4+ T cell proliferation restored significantly.ConclusionsiC3b inhibited the differentiation of CD14+ monocytes into CD1a+ MDDCs via ERK1/2 pathway, and restoration of CD1a+ MDDCs maturation occurred with the treatment of inhibitors specific for ERK1/2 pathway. Meanwhile, treatment of the inhibitor for the ERK1/2 cascade reversed the inhibited CD4+ T cell proliferation, implying a potential possibility for clinical intervention.

► iC3b inhibited maturation of CD1a+ MDDCs from CD14+ monocytes via ERK1/2 pathway.
► CD4+ T cell proliferation was interrupted with iC3b exposure.
► Treatment of ERK1/2 cascade inhibitor restored CD1a+ MDDCs maturation.
► The inhibitor treatment reversed the inhibited CD4+ T cell proliferation.