| Abstrakt: |
The chicken (Gallus gallus), which has three aryl hydrocarbon receptor (AHR) isoforms (ck AHR1, ck AHR2, and ck AHR1β) and two AHR nuclear translocator (ARNT) isoforms (ck ARNT1 and ck ARNT2), is highly sensitive to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and can serve as an avian model to gain an understanding of the mechanism underlying dioxin toxicity. To elucidate the mechanism of TCDD-induced immunotoxicity in avian species, we treated chicken embryos in ovo with graded concentrations of TCDD (1.5, 2.5, 3.0, 3.3, 3.5, and 4.0 μM). Initially, we measured mRNA expression levels of ck AHR and ck ARNT isoforms and analyzed the T cell populations and transcriptome in the thymuses of TCDD-treated chicken embryos. Quantitative polymerase chain reaction analysis revealed that mRNA expressions of ck AHR1 and ck ARNT2 were dominant in the thymus. Severe weight loss and thymus atrophy were observed in the TCDD-treated embryos. Immunophenotyping analyses demonstrated significant increases in CD4+CD8-CD25+ and CD4+CD8+CD25+ regulatory T cells (Tregs) populations following TCDD exposure, suggesting that TCDD suppresses T cell-mediated immune responses in chicken embryos. In addition, thymic transcriptome analyses intimated that alteration of the signaling pathways related to erb-b2 receptor tyrosine kinase 4 (ERBB4) and wnt family member 5A (WNT5A), and bone morphogenetic protein (BMP) may be associated with the TCDD-induced thymus atrophy. We also observed significantly altered expression levels of genes including interleukine 13 receptor subunit alpha 2 (IL13RA2), transforming growth factor beta 1 (TGFβ1), collagen type III alpha 1 chain (COL3A1), and collagen type IX alpha 3 chain (COL9A3), implying immunosuppression, fibrosis development, and collagen deposition. Collectively, these findings suggest that TCDD exposure activates the ck AHR1- ck ARNT2 signaling pathway and suppresses immune responses through the prompted differentiation to CD4+CD8-CD25+ and CD4+CD8+CD25+ Tregs and altered expressions of immune-related genes in the thymus of chicken embryos. • The ckAHR1 and ckARNT2 isoforms might be affected on the mechanism that caused thymic immunotoxicities in chicken. • Alterlation of the ERBB and WNT signaling pathway in Transcriptomic analysis may be associated with thymic malformation. • Inductions of regulatory T cell by TCDD exposure imply that TCDD is a regulator of immune responses in chicken thymus. • This provides insight of the mechanisms that TCDD associated with thymus atrophy and immune suppression in chicken embryo. [ABSTRACT FROM AUTHOR] |
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