AhR ligands differentially affect thymus and peripheral lymphoid organs by targeting T cells and their functions leading to pro- or anti-inflammatory responses

Abstract TCDD, FICZ, and Resveratrol (RES) are potent ligands of aryl hydrocarbon receptor (AhR). TCDD is well known to cause thymic atrophy but the effects of FICZ and RES have not been studied to date. In the current study, we investigated the effect of AhR ligands in vivo. We chose these AhR ligands for their different origin-TCDD, an environmental contaminant, FICZ, endogenously generated, and RES, found in plant products. To this end, C57BL/6 mice were treated with vehicle (corn oil) or TCDD (10 μg/kg bw) or FICZ (10 μg/kg bw) or RES (100 mg/kg bw) by oral gavage. Three days post treatment, thymi and spleens were harvested and stained with fluorochrome-labelled Abs against various T cell surface markers and analyzed by flow cytometry. We observed significant effect of TCDD on decreasing thymic weight and thymic cellularity, when compared to vehicle. FICZ, on the other hand, had no significant effect on thymus. RES, however, significantly caused increase in thymic weight as well as thymic cellularity. Upon analysis of various T cell populations in the thymus, TCDD caused significant downregulation of almost all the markers (CD3, CD4, CD8, CD25, CD44, and αβTCR) whereas, FICZ and RES had moderate effects on thymic T cell subpopulations. Upon analysis of spleen, all the three AhR ligands had mixed effects. We observed significant effect of TCDD and RES in generation of Tregs, when compared to vehicle. FICZ, on the other hand, suppressed Tregs but significantly increased Th17 cells. Together, our studies suggest that although TCDD, FICZ, and RES are AhR ligands, they had different effects on both thymus and spleen. TCDD and RES had role in inducing immune suppression by generating more Tregs, whereas, FICZ had a role in inflammation by generating more Th17 cells.