Aryl hydrocarbon receptor involvement in the Tr1-like cell differentiation and IL10 production induced by aflatoxin B1 individual and combined with fumonisin B1.

RODRIGUEZ, MG; THEUMER, MG; VELEZ, PA; MARY, VS; RUBINSTEIN, HR

CABA

Congreso; Reunión anual de Sociedades de Biociencias SAIC-SAI-SAFIS 2020.; 2020

SAIC-SAI-SAFIS

Co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequent in nature, and has been associated with a high incidence of human hepatocellular carcinoma. AFB1 toxicity is related with its metabolization by cytochrome P450 1A (CYP1A), which is induced by aryl hydrocarbon receptor (AhR) activation. AhR participates in immune tolerance control, regulating the differentiation of T cells to Tr1 or Treg regulatory cells, among other mechanisms. Hence, this work was aimed to assess probable changes in Tr1-like cell differentiation due to AFB1 and FB1 exposures, and the AhR involvement in such effects. Spleen mononuclear cells (SMC) from mice with different AhR affinities (C57BL/6 and B6.D2N-Ahrd/J; background C57BL/6), were incubated up to 72 h with AFB1 (0-50 μM), FB1 (0-250 μM) and both-toxin mixtures. Later, Tr1-like cell (CD4+, Foxp3-, CD25-, IL10+) percentages stimulated by TGFβ + IL27 and intracellular IL10 (flow cytometry in both cases), IL10 in culture supernatants (ELISA), and the CYP1A and AhR mRNA levels (qRT-PCR), were assessed.AFB1 and its mixtures increased CYP1A and AhR mRNA levels, being greater in the latter; whilst FB1 did not produce changes. These data were correlated with the highest toxicities caused by the toxin mixtures. Tr1-like cell differentiation were raised by both, AFB1 and FB1, altough in a AhR-dependent way, or independently of AhR and TGFB + IL27, respectively. IL10 was increased only by AFB1. However, the mycotoxin mixtures did not modify the Tr1-like cell percentages, altough they decreased the IL10 production under basal and Tr1-stimulating conditions in an AhR-dependent manner. In conclusion, AhR is involved in the immunosuppressive effects of AFB1, and in the immunotoxicity induced by the AFB1-FB1 mixtures; but is not implicated in the immunoregulatory effects of FB1.In conclusion, AhR is involved in the immunotoxicity of AFB1 and AFB1-FB1 mixtures; but is not implicated in the immunoregulatory effects of FB1.