Abstract
Inflammatory bowel disease (IBD) is associated with loss of immune tolerance to antigens originating from the diet and from the gut microflora. T cells play crucial roles in the pathogenesis of IBD. Chlorpyrifos (CPF) is one of the most ubiquitous organophosphate pesticides in the world. The aim of the study was to investigate the effects of dietary exposure to CPF on T-cell populations in C57BL/6 mice with dextran sulfate sodium (DSS)-induced colitis. Mice received distilled water containing 3% DSS for 6 days to induce acute colitis, which was then replaced with distilled water for 21 days, allowing progression to chronic inflammation. During the experimental period, mice were given either an AIN-93-based control diet or a CPF diet-containing 7, 17.5, or 35 ppm of CPF. Results showed that dietary exposure to CPF significantly increased circulating neutrophils in colitic mice. CPF-exposed groups had lower percentages of blood and spleen T cells without altering the proportions of CD4+ and CD8+ T-cell subsets. The percentage of blood regulatory T (Treg) cells, as well as splenic expressions of Treg-related genes, were suppressed in CPF-exposed mice. CPF upregulated the colonic gene expression of tumor necrosis factor-α. Meanwhile, plasma haptoglobin, colon weights, and luminal immunoglobulin G levels were higher in CPF-exposed groups. Histopathological analyses also observed that colon injury was more severe in all CPF-exposed mice. These results suggest that dietary exposure to CPF aggravated tissue injuries in mice with DSS-induced chronic colitis by suppressing T-cell populations and Treg polarization.
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Acknowledgements
This work was supported by research grants from Taipei Medical University (TMU105-AE1-B16) and the Ministry of Science and Technology, Taipei, Taiwan (MOST 107-2314-B-038-100-MY3). The authors acknowledge the technical support provided by the TMU Core Facility.
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Huang, HM., Pai, MH., Yeh, SL. et al. Dietary exposure to chlorpyrifos inhibits the polarization of regulatory T cells in C57BL/6 mice with dextran sulfate sodium-induced colitis. Arch Toxicol 94, 141–150 (2020). https://doi.org/10.1007/s00204-019-02615-2
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DOI: https://doi.org/10.1007/s00204-019-02615-2