Conjugated linoleic acid suppresses dendritic cell activation and subsequent Th17 responses

摘要

PUFAs (polyunsaturated fatty acids) can modify immune responses, so they may have potential therapeutic effects in inflammatory disorders. We previously demonstrated that the cis-9, trans-11 isomer of the PUFA conjugated linoleic acid (CIA) can modulate dendritic cell (DC) cytokine production. Since DCs play a central role in initiating inflammation by directing T helper (Th) cell differentiation, here we examined the effects of CIA on DC maturation and migration and the subsequent generation of Th cell responses. We examined the effect of CIA in vitro on the function of lipopolysaccharide (LPS)-activated bone marrowderived DCs and ex vivo using cells from mice with high levels of CIA in their diet. We report that CIA inhibits DC migration and modulates TLR-induced production of key cytokines involved in Th cell differentiation both in vitro and in vivo. These changes were accompanied by a significant decrease in expression of MHCII, CD80 and CD86 on the DC surface. Exposure of DCs to CIA suppressed their ability to promote differentiation of naive T cells into Thl and/or Th17 cells in vitro and following their adoptive transfer in vivo. Furthermore, in a murine model of endotoxic shock, treatment with CIA suppressed LPS-induced induction of circulating IFN-gamma, IL-12p40 and IL-1 beta. This is the first study to demonstrate that exposure of antigen-presenting cells to CIA can modulate the subsequent Th cell response, and the findings may explain some of the beneficial effects of c9, t11-CIA in inflammatory diseases mediated by Th1 and Th17 cells. (C) 2014 Elsevier Inc. All rights reserved.