TLR4-dependent effects of ISAg treatment on conventional T cell polarization in vivo

Anim Cells Syst (Seoul). 2019 Apr 25;23(3):184-191. doi: 10.1080/19768354.2019.1610059. eCollection 2019 Jun.

Abstract

We recently demonstrated that the polysaccharide component of the Korean medicinal herb Angelica gigas (immuno-stimulatory fraction of A. gigas; ISAg) induces anticancer effects in mice by activating natural killer (NK) and natural killer T (NKT) cells. However, it is unclear whether the use of ISAg in vivo can affect the differentiation of conventional T cells. Here, we investigated the effects of ISAg on the activation of conventional CD4+ and CD8+ T cells. We found that the administration of ISAg induced the polarization of CD4+ T cells toward the acquisition of the Th1 phenotype in vivo. Additionally, in mice treated with ISAg, CD8+ T cells produced more IFNγ than in control mice treated with PBS. Moreover, treatment with ISAg activated CD4+ and CD8+ T cells as well as NK and NKT cells, resulting in the secretion of Th1-type cytokines in a toll-like receptor 4 (TLR4)-dependent manner, implying that TLR4 is critical for an optimal Th1 response. Interestingly, ISAg treatment increased the number of Foxp3+ Treg cells, but not of Th2 cells, compared to control mice treated with PBS, indicating that ISAg possesses an immunomodulatory capacity that can control adaptive immune responses. Taken together, our results indicate that ISAg possesses a Th1-enhancing activity that could be used to treat Th2-mediated allergic immune diseases such as atopic dermatitis.

Keywords: Angelica gigas; TLR4; Th1 polarization; Treg cells.

Grants and funding

This work was supported by the Ministry of SMEs and Startups and the Korea Institute for Advancement of Technology under a Research and Development for Regional Industry Grant #R0003864 to SHJ and SJP.