Abstract
Contamination with fumonisins produced by Fusarium spp. is rapidly growing in both developing and developed countries. The purpose of this study was to determine whether oral exposure to fumonisin contributed to the development of allergic diseases. We initially examined the immunotoxic potential of short-term, oral administration of fumonisin B1 (FB1, 1 mg/kg) and fumonisin B2 (FB2, 1 mg/kg), both naturally occurring fumonisins, using a BALB/c mouse model of allergic contact dermatitis and Dermatophagoides farina-induced asthma. Using an NC/nga mouse model of atopic dermatitis (AD), we evaluated the adverse effects of subchronic oral exposure to low concentrations of FB2 (2 or 200 μg/kg). Finally, we explored the influence of FB2 on regulatory T cell proliferation and function in mesenteric lymph nodes after 1-week oral exposure to FB2 in BALB/c mice. Oral exposure to FB2 markedly exacerbated the symptoms of allergy, including skin thickness, histological evaluation, immunocyte proliferation, and proinflammatory cytokine production, although no change was observed following exposure to FB1. Furthermore, oral exposure to low concentrations of FB2 considerably exacerbated the AD scores, skin thickness, transepidermal water loss, histological features, and proinflammatory cytokine production. The aggravated allergic symptoms induced by oral exposure to FB2 could be attributed to the direct inhibition of IL-10 production by regulatory T cells in mesenteric lymph nodes. Our findings indicate that the recommended maximum fumonisin level should be reconsidered based on the potential for allergy development.
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We thank Editage (www.editage.jp) for English language editing.
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A part of this study was funded by the grant-in-aid for scientific research of The Tojuro Iijima Foundation for Food Science and Technology.
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Conceptualization: TF. Methodology: MA, HY, AM, NI, YT, MN, TY, and TF. Formal analysis and investigation: MA and TF. Writing—original draft preparation: MA and TF. Writing—review and editing: MA, HY, AM, NI, YT, MN, TY, and TF. Funding acquisition: TF.
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Supplementary file1 Supplemental Fig. 1 Experimental protocol used to generate mouse models of allergic contact dermatitis (A), asthma (B), and atopic dermatitis (C) (JPG 1615 KB)
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Supplementary file2 Supplemental Fig. 2 Impact of oral exposure to FB1 and FB2 on the reproducibility of a mouse model of allergic contact dermatitis. Oral exposure to FB2 significantly increases the ear swelling response (A). Representative histological image of affected skin in each group (B). Number of CD11c+CD40+ DCs (C), CD3+CD4+ T cells (D), and CD19+IgE+ B cells (E) in the auricular LNs. There is no significant change in serum levels of IgE (F). FB2 exposure upregulated IL-4 (G) and IL-13 (H) production in LNs. Bar = 100 μm. Each result is presented as the mean ± standard error of the mean (SEM). FB1, fumonisin B1; FB2, fumonisin B2; DCs, dendritic cells; LNs, lymph nodes; IL, interleukin (JPG 1282 KB)
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Supplementary file3 Supplemental Fig. 3 Exposure to fumonisin B2 (FB2) did not alter the cytokine production by stimulated THP-1 (A), human keratinocytes (HaCaT) (B), or human bronchial epithelium (BEAS-2B) (C). Each result is presented as the mean ± standard error of the mean (SEM) (JPG 629 KB)
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Ando, M., Yamaguchi, H., Morimoto, A. et al. Chronic oral exposure to low-concentration fumonisin B2 significantly exacerbates the inflammatory responses of allergies in mice via inhibition of IL-10 release by regulatory T cells in gut-associated lymphoid tissue. Arch Toxicol 97, 2707–2719 (2023). https://doi.org/10.1007/s00204-023-03579-0
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DOI: https://doi.org/10.1007/s00204-023-03579-0