Interplay of Vitamin D and Aryl Hydrocarbon Receptors in CD4+ T Cell Fate Determination

It seems that vitamin D receptor (VDR) and aryl hydrocarbon receptor (AHR) are important receptors that determine the fate of CD4+ T cell differentiations under various physiological and pathophysiological conditions. Herein, we aim to investigate the potential effects of VDR and AHR ligands on the differentiation of CD4+ T-cells. Male C57BL/6 mice, were treated with an endogenous ligand of AHR 6-formylindolo[3,2-b] carbazole (FICZ), and an AHR antagonist known as CH223191 via intraperitoneal injection, either individually or in combination with Vitamin D3. After 6 days, the mice were killed, and their spleen cells were isolated and analyzed using flow cytometry. Additionally, the ligand binding domain (LBD) of the AHR was modeled using Modeler software, while the molecular docking was performed by AutoDock 1.5.4. Our findings also showed that the AHR antagonist CH223191 increased the prevalence of Th1 cells and altered the Th1/Treg and Th1/Th2 cell ratios. Additionally, the combination of FICZ and Vitamin D3 led to an increase in Th17 and Th2 cells. The molecular docking analysis shows that Vitamin D3 was well accommodated within the binding site of AHR. Molecular docking analysis suggests that vitamin D3 could act as a potential ligand for the AHR. AHR ligands reduce the populations of Th1, Th2, and Treg cells while promoting Th17 differentiation. Furthermore, FICZ alone or in combination with vitamin D3 enhances the differentiation of Th2 and Th17 cells.