Here we investigated how allergens and lectins modulate the TLR4-AhR-IDO axis in human monocyte-derived DCs.
Using a combination of genomics, proteomics, and immunologic studies, we investigated the role of MR and AhR in IDO regulation and its effect on T helper cell differentiation.
We have demonstrated that LPS induces both IDO isoforms (IDO1 and IDO2) in DCs, with partial involvement of AhR. Additionally, we found that, like mannan, different airborne allergens can effectively downregulate TLR4-induced IDO1 and IDO2 expression, most likely through binding to the MR. Mannose-based ligands were also able to downregulate IL-12p70 production by DCs, affecting T helper cell polarization. Interestingly, AhR and some components of the noncanonical nuclear factor κB pathway were shown to be downregulated after MR engagement, which could explain the regulatory effects of MR on IDO expression.
Our work demonstrates a key role for MR in the modulation of the TLR4-AhR-IDO axis, which has a significant effect on DC behavior and the development of immune responses against allergens.