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

We have previously shown that root extracts fromAnthriscus sylvestris(AS) can stimulate antigen-presenting cells such as dendritic cells and macrophages, which implies thatASextract can be useful as an immune adjuvant to promote the immune response. Here, we investigated thein vivoeffect ofASextract on CD4+T cell differentiation using the DO11.10 ovalbumin (OVA)-specific TCR transgenic mouse model. We found that the repeated injection ofASextract 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 uponASstimulation. In addition, natural killer T (NKT) cells and neutrophils were activated to produce IL17 inASextract-treated mice. Furthermore,in vivotreatment withASextract significantly decreased the frequency of Foxp3+CD25+inducible Treg cells compared to the vehicle-treated control group. Taken together, our findings suggest thatin vivotreatment withASextract 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 thatAS-derived extract might be useful as an adjuvant to treat Th2-biased immune diseases such as atopic dermatitis. [ABSTRACT FROM PUBLISHER]