Anthriscus sylvestris-derived extract induces Th1 and Th17 cell differentiation via the upregulation of IL12 and IL23 production

Abstract

We have previously shown that root extracts from Anthriscus sylvestris (AS) can stimulate antigen-presenting cells such as dendritic cells and macrophages, which implies that AS extract can be useful as an immune adjuvant to promote the immune response. Here, we investigated the in vivo effect of AS extract on CD4+ T cell differentiation using the DO11.10 ovalbumin (OVA)-specific TCR transgenic mouse model. We found that the repeated injection of AS extract plus OVA antigens resulted in increases in both the Th1-polarizing IL12 and Th17-polarizing IL23 cytokines on macrophages. Consistent with the upregulation of IL12 and IL23, both IFNγ-producing Th1 and IL17-producing Th17 cells specific for OVA antigens were significantly induced upon AS stimulation. In addition, natural killer T (NKT) cells and neutrophils were activated to produce IL17 in AS extract-treated mice. Furthermore, in vivo treatment with AS extract significantly decreased the frequency of Foxp3+CD25+ inducible Treg cells compared to the vehicle-treated control group. Taken together, our findings suggest that in vivo treatment with AS extract induces proinflammatory cytokine production by macrophages, leading to the activation of IL17-producing innate immune cells such as NKT cells and neutrophils, presumably at early time points and later, as well as the induction of IFNγ- or IL17-producing adaptive immune cells such as Th1 and Th17 cells with the concomitant downregulation of Treg cells. These findings imply that AS-derived extract might be useful as an adjuvant to treat Th2-biased immune diseases such as atopic dermatitis.