Effects of mammalian target of rapamycin and aryl hydrocarbon receptor‐mediating autophagy signaling on the balance of Th17/Treg cells during perinatal bisphenol A exposure in female offspring mice

Abstract

Bisphenol A (BPA)'s immunotoxic properties have received increasing interest, which can lead to immune dysfunction and related disease development. However, the mechanism is not completely clear. A growing body of evidence suggests that autophagy has important roles in innate immunity, inflammatory response, and adaptive immunity. This study aimed to investigate the possible mechanisms of mammalian target of rapamycin (mTOR), aryl hydrocarbon receptor (AhR), and autophagy in Treg/Th17 imbalance induced by perinatal BPA exposure. Our results showed that the number of Th17 cells in the spleen of offspring female mice significantly increased, while the number of Treg cells decreased significantly, which was consistent with the expression levels of up‐regulation of RORγt protein and a down‐regulation Foxp3 protein. The levels of mTOR, p‐mTOR, P62, and AhR protein expression increased, and LC3 protein decreased in spleen. However, in the thymus, we found that RORγt and Foxp3 proteins changed most significantly in the low‐dose BPA group, and the same as p‐mTOR and P62 protein levels. We conjectured that the potential mechanism of the imbalance of Th17/Treg upon perinatal exposure to BPA was probably associated with autophagy dysfunction. Proper autophagy plays an important role in maintaining the homeostasis of the thymic and spleen immune system.

Blimp1 suppressed CD4+ T cells‐induced activation of fibroblast‐like synoviocytes by upregulating IL‐10 via the rho pathway

“…By producing a variety of pro‐inflammatory factors, CD4 + T cells exert key effects in the pathogenesis of RA 3 . After exposure to the antigen stimulation, naive CD4 + T cells differentiate into T cell subsets, including regulatory T cells (Tregs), T helper 17 (Th17) and T helper 1 (Th1), which are characterized by lineage‐specific expression of transcription factors and proinflammatory cytokines 4,5 . In RA, fibroblast‐like synoviocytes (FLSs) become activated, hyperplastic and anti‐apoptotic, and they secrete many cytokines and chemokines.…”

“…3 After exposure to the antigen stimulation, naive CD4 + T cells differentiate into T cell subsets, including regulatory T cells (Tregs), T helper 17 (Th17) and T helper 1 (Th1), which are characterized by lineagespecific expression of transcription factors and proinflammatory cytokines. 4,5 In RA, fibroblast-like synoviocytes (FLSs) become activated, hyperplastic and anti-apoptotic, and they secrete many cytokines and chemokines. These inflammatory mediators promote the recruitment of immune cells (including T cells) to the synovium.…”

2,2′,4,4′‐Tetrabromodiphenyl ether and cadmium co‐exposure activates aryl hydrocarbon receptor pathway to induce ROS and GSDME‐dependent pyroptosis in renal tubular epithelial cells

“…7 Aryl hydrocarbon receptor (AhR), a nuclear transcription factor activated by ligands, plays an important role in health and disease development in response to environmental stimuli. 8 Initially localized in the cytosol, AhR binds to heat shock protein 90 (Hsp90), co-chaperone protein p23 (p23), AhR interacting protein (AIP), and c-Src tyrosine kinase (c-SRC). Upon ligand binding, such as environmental toxins, AhR undergoes a conformational change that facilitates the nuclear translocation of the AhR-ligand complex.…”