**Conflict of interest**

There is no conflict of interest in this study.

*Role of Aryl Hydrocarbon-Ligands in the Regulation of Autoimmunity DOI: http://dx.doi.org/10.5772/intechopen.80840*

*Immune Response Activation and Immunomodulation*

and induce Foxp3+

injection may be more effective.

IDO expression was found to be increased in DCs by TCDD or FICZ [38]. The conversion of Treg to Th17 and Th17 to Th1 profiles has been reported and reprogramming of subsets might be possible by additional cytokine provision, such as IL-23, IL-6, or removal of reinforcement factors, such as IL-23 or AhR-ligands [38]. The reported ability of IDO products (i.e., tryptophan metabolites) to suppress ROR-γt

to an IL-10-producing subset might result during exposure to some AhR-ligands. Since some AhR-ligand treatments lead to Th17 responses in the absence of Treg responses, allowing enhanced autoimmunity, this suggests that these ligands may be useful to promote antitumor immunity. It also raises the possibility that the anticancer effects of curcumin and quercetin may be due to their ability to promote potent effector T cell subsets in addition to suppressing some chronic inflammatory states. Another potentially beneficial use of AhR-ligands that have the ability to increase Treg populations is for the prevention or treatment of autoimmune diseases.

Experimental evidence has shown that flavonoids could be used to treat many diseases including cancer [59, 60]. The administration of curcumin was found to block the formation of lesions and tumors in C57Bl/6J mice after implanting murine melanoma B16F10 cells in their neck and brain. Furthermore, curcumin treatment was observed to significantly inhibit the proliferation of PC-3 prostate tumor cells. The proposed mechanism for this effect of curcumin was its ability to significantly suppress NF-ĸB and AP-1 signaling pathways in tumor cells [61, 62]. Curcumin was given orally at concentrations in the micro-molar range; however, results showed that the concentration of curcumin was in the nano-molar range in the plasma [63, 64], due to the extensive metabolism of curcumin in the intestine and liver, which prevents the maintenance of high concentration of curcumin in the plasma and tissues after taking it orally [65, 66]. The curcumin is effective on the cancer cells at high concentration which is difficult to be maintained for several hours even in the gastrointestinal tract [63]. This suggests that the potential of using curcumin for cancer treatment is limited when given orally and the intraperitoneal

In contrast, other studies have shown that high concentrations of curcumin were found to enhance chromosome malformation in different cell lines. The curcumin could cause DNA damage both *in vivo* and *in vitro* and increase the incidence of thyroid gland follicular cell hyperplasia and carcinogenic activity in the small intestine [67–69]. This was proposed mainly due to its ability to increase the production of reactive oxygen species (ROS) [70]. Other studies have shown that curcumin has the ability to suppress cytochrome P450 enzyme, glutathione, S-transferase, and UDPglucuronosyltransferase, causing toxicity due to the increased level of drugs in the plasma [71]. Although lower concentrations of curcumin could enhance antioxidant activity, high concentrations of curcumin have shown pro-oxidant effects [63, 72]. Similarly, quercetin is known as an antioxidant, anti-inflammatory, and antimicrobial compound at low doses [73, 74]. In contrast, quercetin can enhance the production of ROS at higher concentrations [75]. ROS production by quercetin was found to kill some cancer cells, and quercetin complexes with bioactive compounds and metal ions such as lanthanum was reported to have powerful cytotoxic and antitumor properties at a concentration in the range of 100–1000 mM and the exposure time of tumor cells was around 3 hours. A quercetin/lanthanum complex was found to have a genotoxic effect on human cervical carcinoma cells due to ROS production [76].

Treg cells [58] may indicate Th17 to Treg conversion, or shift

**158**

**Conflict of interest**

There is no conflict of interest in this study.
