EDC-induced mechanisms of immunotoxicity: a systematic review

Abstract

Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in alteration of homeostasis, reproductive, and developmental, and immune system impairments. The immunotoxicity of EDCs involves many mechanisms altering gene expression that depend on the activation of nuclear receptors such as the aryl hydrocarbon receptor (AHR), the estrogen receptor (ER), and the peroxisome proliferator-activated receptor (PPAR), which also results in skin and intestinal disorders, microbiota alterations and inflammatory diseases. This systematic review aims to review different mechanisms of immunotoxicity and immunomodulation of T cells, focusing on T regulatory (Treg) and Th17 subsets, B cells, and dendritic cells (DCs) caused by specific EDCs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), bisphenols (BPs) and polyfluoroalkyl substances (PFASs). To achieve this objective, a systematic study was conducted searching various databases including PubMed and Scopus to find in-vitro, in-vivo, and biomonitoring studies that examine EDC-dependent mechanisms of immunotoxicity. While doing the systematic review, we found species-and cell-specific outcomes and a translational gap between in-vitro and in-vivo experiments. Finally, an adverse outcome pathway (AOP) framework is proposed, which explains mechanistically toxicity endpoints emerging from different EDCs having similar key events and can help to improve our understanding of EDCs mechanisms of immunotoxicity. In conclusion, this review provides insights into the mechanisms of immunotoxicity mediated by EDCs and will help to improve human health risk assessment.

Role of microRNA in Endocrine Disruptor-Induced Immunomodulation of Metabolic Health

“…On the other hand, the role of miRs in regulation of inflammation-related genes, especially during the development of metabolic diseases, is described in many studies listed in Table 1. The above isolated findings show a significant correlation between miRs and EDCs induced immunomodulation during metabolic disease progression, as we have seen rapid growth in the number of studies focusing on the effect of EDCs on immunity via miR regulation [78,88]. Inhibit adipogenesis [94]; Protect β cell function [95]; Improve glucose metabolism and inhibit hepatic steatosis [96] miR-21…”

A review on immunomodulatory effects of BPA analogues

“…T lymphocytes are an important component of the adaptive part of the immune system, and consequently, dysfunction at any level of differentiation into subsets [e.g., CTL, Th1, Th2, Th9, fTh, Th17, and regulatory T cells (Treg) (Moser and Leo 2010 ; Chraa et al 2019 )] by endocrine disruptors such as bisphenols have significant consequences for normal immune function (Malaisé et al 2020a ; Malaisé et al 2021 ; Dong et al 2020 ; Gao et al 2020 ; Sabuz Vidal et al 2021 ).…”

Endokrin Bozucuların İmmün Sistem ve İnflamasyon Üzerine Etkileri

“…Endokrin bozucular (EB); etkilerini sıklıkla steroid hormonlar ya da peptid/protein yapıda hormonlar üzerinden gösterirler ve hormon faaliyetlerinin herhangi bir yönünü bozabilirler. EB'ler major etki mekanizması, bunların steroid hormonları (östrojen, androjen, adrenal hormonlar), tiroid reseptörleri, PPAR (peroksizom aktive reseptör) ve aril hidrokarbon reseptörleri (AhR) ile etkileşimi yoluyla gerçekleşmektedir (Sabuz Vidal, Deepika, Schuhmacher, & Kumar, 2022). Spesifik bir immünomodülasyon ve immünotoksisite mekanizması AHR'nin EB'ler tarafından etkinleştirilmesidir.…”