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• PBMCs of endometriosis patients express lower levels of AHR and IDO1 genes compared to those of normal individuals. • TCDD increases the expression of AHR, IDO1 and FOXP3 genes in endometriosis compared to non-endometriosis PBMCs. • In response to TCDD treatment, endometriosis PBMCs produce higher levels of kynurenine and IL-6. Endometriosis happens following the implantation of endometrial-derived tissues outside the uterine cavity. It has been suggested that 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) is involved in endometriosis development. Furthermore, aryl hydrocarbon receptor (AHR), as a TCDD receptor, has been demonstrated to regulate immune responses. Nonetheless, data regarding the mechanisms, through which TCDD influences the immune system in endometriosis, are still inconclusive. Therefore, frequency of regulatory T cells (Tregs) and the expression of FOXP3 , AHR and indoleamine 2, 3-dioxygenase 1 (IDO1) from endometriosis and non-endometriosis individuals were investigated in the absence and presence of TCDD; also, the concentration of IL-6 and kynurenine in the supernatant of cultures was assessed. The impact of TCDD-treated PBMCs on the migration capacity of menstrual blood-derived stromal stem cells (MenSCs) and monocyte chemoattractant protein-1 (MCP-1) and IL-6 production was determined. Here, we found that AHR and IDO1 expression levels were lower in endometriosis PBMCs; however, TCDD treatment increased AHR , FOXP3 , IDO1 , IL-6, and Treg levels in the endometriosis group (P ≤ 0.05−0.0001). TCDD-treated PBMCs increased the migration capacity of MenSCs and up-regulated MCP-1 and IL-6 levels in the PBMCs/MenSCs co-culture (P ≤ 0.01−0.0001). In conclusion, these results shed light on the probable mechanisms, through which AHR activation by chemical toxicants can impact inflammatory immune mediators involved in the development of endometriosis; also, these data support the idea that TCDD could promote endometriosis progression. [ABSTRACT FROM AUTHOR]

• MenSCs downregulate RORC and inhibit T CD4 + TH17 polarization. • MenSCs managed to generate Tregs in a TH17 favored condition. • Inhibition of PGE2 synergize with the capacity of MenSCs to hinder TH17 differentiation. • MenSCs produce a considerable amount of IDO and increased Treg/Th17 ratio. Uncontrolled TH17 differentiation has been suggested to play a role in the pathogenesis of pregnancy loss. We recently showed that menstrual blood stromal/stem cells (MenSCs) alter functional features of natural killer cells. Here, we hypothesized that MenSCs could modulate differentiation of TH17 cells. MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. TH17 polarization and proliferation of purified T CD4+ cells were assessed by flow cytometry in a well-defined co-culture system containing T CD4+ cells and MenSCs or BMSCs. Indoleamine 2,3-Dioxygenase (IDO) activity was evaluated in MenSC and BMSC culture supernatants by a colorimetric assay. The impact of MenSCs on expression of transcription factors, RORC, T-bet, Gata3, NRP-1 and Helios were studied by qPCR. MenSCs significantly inhibited TH17 differentiation (p = 0.0383) and percentage of the cells co-expressing IL-17 and IFN-γ (p = 0.0023). PGE2 blockade significantly reduced percentage and proliferation of T CD4+IL-17+ (p = 0.003, p = 0.0018), T CD4+ IFN-γ+ (p = 0.002, p = 0.0022) and T CD4+IL-17+ IFN-γ+ (p = 0.004, p = 0.02) cells. MenSCs produced a considerable activity of IDO (p = 0.0002), induced a significant rise in the Treg frequency (p = 0.0091) and a sharp increase in TH17/Tregs ratio (p = 0.0022). MenSCs increased expression of NRP1 (p = 0.001), while downregulated expression of RORC in T cells (p = 0.001). Our results suggest a supportive role for MenSCs in establishing a pregnancy-friendly microenvironment in the uterus and put forth the idea that inherent abnormalities of MenSCs may be a basis for dysregulated endometrial immune network leading to pregnancy loss. [ABSTRACT FROM AUTHOR]