TNFα and TGF-β1 influence IL-18-induced IFNγ production through regulation of IL-18 receptor and T-bet expression

Abstract

Bacterial infections can lead to a state of uncontrolled inflammation and also trigger autoimmune disease. At the centre of this are CD4+ T cell responses in inflammatory tissues or local lymph nodes which are orchestrated by dendritic cells. IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNγ production. In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNγ production induced by IL-18 is potentiated (>5-fold) by TNFα and completely suppressed by TGF-β1. IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNγ production. The mechanism through which TNF..