Environmental contaminants (ECs) are associated with pathogenesis and etiology of numerous chronic diseases. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor is the intracellular mediator of the EC effects (Busbee et al., 2013). Various studies have shown that AhR activation induces T-cell disequilibrium that could lead to autoimmunity. We aimed to study the impact of AhR activation in medullary thymic epithelial cells that are essential for central tolerance mechanisms and T-cell differentiation. Here, we analyze the effect of AhR activation by either its exogenous ligand (2,3,7,8-Tetrachlorodibenzodioxin (TCCD), and Benz[a]pyrene (BAP)) or its endogenous ligand (6-Formylindolo (3,2-b)carbazole (FICZ)), in vitro on the homeostasis and physiological function (expression of immune tolerance key factors, cytokines and chemokines) of primo-cultured human thymic epithelial cells (TECs). All the studies on human thymuses were approved by the local Ethics Committee (CCP, Ile de France-Paris 7, agreement N°C09-36). P values were obtained using the 1-way ANOVA test. *P < 0.05; **P < 0.001; ***P < 0.0001 3-AHR ligands deregulate cytokine expression in primary human cultured TECs AhR ligands (endogenous FICZ, and exogenous BAP and TCDD) modulate in TECs, the expression of cytokines involved in the regulation of T-cell differentiation and Th17/ Treg cell balance. By contrast, only exogenous AhR ligands (TCDD and BAP) modified B cell chemokine attractant CXCL13 expression in primary human TECs (n>7).