Co-exposure to aflatoxinB1 (AFB1) and fumonisin B1 (FB1) isfrequent in nature, and has been associated with a high incidence of humanhepatocellular carcinoma. AFB1 toxicity is related with its metabolizationby cytochrome P450 1A (CYP1A), which is induced by aryl hydrocarbon receptor(AhR) activation. AhR participates in immune tolerance control, regulating thedifferentiation of T cells to Tr1 or Treg regulatory T cells, among othermechanisms. Hence, this work was aimed to assess probable changes in Tr1-likecell differentiation due to AFB1 and FB1 exposures, andthe AhR involvement in such effects. Spleen mononuclear cells (SMC) from micewith different AhR affinities (C57BL/6 and B6.D2N-Ahrd/J; background C57BL/6), were incubated upto 72 h with AFB1 (0, 5, 25 and 50 μM), FB1 (0, 25, 125and 250 μM) and both-toxin mixtures. Later, Tr1-like cell (CD4+,Foxp3-, CD25low/-, IL10+) percentagesstimulated by TGFβ + IL27 and intracellular IL10 (flow cytometry in bothcases), IL10 in culture supernatants (ELISA), and the CYP1A and AhR mRNA levels(qRT-PCR), were assessed.
AFB1 andits mixtures increased CYP1A and AhR mRNA levels, being greater in the latter;whilst FB1 did not produce changes. These data were correlated withthe highest toxicities caused by the toxin mixtures. Tr1-like celldifferentiation were raised by both, AFB1 (25 μM) and FB1(125 and 250 μM), although in a AhR-dependent way, or independently of AhR andTGFB + IL27, respectively. AhR was also involved in the IL10 raise, which wasaltered only by AFB1. However, the mycotoxin mixtures did not modifythe Tr1-like cell percentage, although they decreased the IL10 production underbasal and Tr1-stimulating conditions in an AhR-dependent manner. In conclusion,AhR is involved in the immunosuppression caused by AFB1, and in theimmunotoxicity induced by the AFB1-FB1 mixtures; but isnot implicated in the FB1 effects on Tr1-like cells.