Aryl hydrocarbon receptor involvement in the tr1-like cell differentiation and IL10 production induced by aflatoxin B1 individual and combined with fumonisin B1.

MARY, VERÓNICA SOFÍA; RODRIGUEZ, MARÍA GISEL; VELEZ, PILAR ANDREA; RUBINSTEIN, HÉCTOR RAMÓN; THEUMER, MARTÍN GUSTAVO

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA, SOCIEDAD ARGENTINA DE INMUNOLOGÍA, SOCIEDAD ARGENTINA DE FISIOLOGÍA.

Co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is frequent in nature, and has been associated with a high incidence of humanhepato cellular 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 T 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 C57BL/6), were incubated up to 72 h with AFB1 (0, 5, 25 and 50 μM), FB1 (0, 25, 125 and 250 μM) and both-toxin mixtures. Later, Tr1-like cell (CD4+, Foxp3-, CD25low/-, IL10+) percentagestimulated 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 (25 μM) and FB1 (125 and 250 μM), although in a AhR-dependent way, or independently of AhR and TGFB + IL27, respectively. AhR was also involved in the IL10 raise, which was altered only by AFB1. However, the mycotoxin mixtures did not modify the Tr1-like cell percentage, although they decreased the IL10 production under basal and Tr1-stimulating conditions in an AhR-dependent manner. In conclusion, AhR is involved in the immunosuppression caused by AFB1, and in the immunotoxicity induced by the AFB1-FB1 mixtures; but is not implicated in the FB1 effects on Tr1-like cells.