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IL-9-Producing Th9 Cells Participate in the Occurrence and Development of Iodine-Induced Autoimmune Thyroiditis

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Abstract

Iodine excess may cause and aggravate autoimmune thyroiditis (AIT), which is regarded as a typical kind of autoimmune disease mainly mediated by CD4+ T cells. Thus far, it is unclear whether T helper (Th) 9 cells, a novel subpopulation of CD4+ T cells, play a potential role in AIT. Therefore, in the present study, changes in Th9 cells were detected in murine models of AIT induced by excess iodine intake to explore the possible immune mechanism. Female C57BL/6 mice were divided into 7 groups (n = 8) and were supplied with water containing 0.005% sodium iodide for 0, 2, 4, 6, 8, 10, and 12 weeks. With the extension of the high-iodine intake duration, the incidence of thyroiditis and the spleen index were significantly increased, and serum thyroglobulin antibody (TgAb) titers and interleukin 9 (IL-9, major cytokine from Th9 cells) concentrations were also increased. Additionally, it was revealed that the percentages of Th9 cells in spleen mononuclear cells (SMCs) and thyroid tissues were both markedly elevated and accompanied by increased mRNA and protein expression of IL-9 and key transcription factors of Th9 cells (PU.1 and IRF-4). Significantly, dynamic changes in Th9 cells were found, with a peak at 8 weeks after high iodine intake, the time point when thyroiditis was the most serious. Importantly, Th9 cells were detected in the areas of infiltrating lymphocytes in thyroid sections. In conclusion, the continuously increasing proportions of Th9 cells may play an important role in the occurrence and development of AIT induced by high iodine intake.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by grants from the Natural Science Foundation of Shandong Province (no. ZR2013HM049, ZR2022MH175), Medical Science and Technology Development Project of Shandong Province (no. 2015WS0485), Reserve Leading Talents Project of Binzhou Medical University Hospital (no. JC2019-03), Scientific Research and Innovation Team Project of Binzhou Medical University Hospital (no. 202031), and Innovation Program of Post-graduate Education of Shandong Province (no. 20038612).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, No. 661 Second Huanghe Road, Binzhou, 256603, China

    Yiwen Li, Hao Liu, Chengyan He & Haibo Xue

  2. Department of Dermatology, Binzhou Medical University Hospital, No. 661 Second Huanghe Road, Binzhou, 256603, China

    Yawen Lin & Lei Ma

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  1. Yiwen Li
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  2. Hao Liu
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  3. Chengyan He
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Contributions

Yiwen Li was responsible for carrying out the experiments, analyzing the data, and writing the manuscript. Hao Liu and Chengyan He were responsible for carrying out the experiments. Yawen Lin participated in carrying out the experiments and data analysis. Lei Ma and Haibo Xue were responsible for the design of the study and reviewed and edited this article. All authors commented on previous versions of the manuscript and approved the final manuscript.

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Correspondence to Haibo Xue.

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The present study was approved (approval no. 20210808–54) by the Laboratory Animal Ethics Committee of Binzhou Medical University Hospital (Binzhou, China). All procedures performed in the present study involving animals were in accordance with the ethical standards of the institution.

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Li, Y., Liu, H., He, C. et al. IL-9-Producing Th9 Cells Participate in the Occurrence and Development of Iodine-Induced Autoimmune Thyroiditis. Biol Trace Elem Res 201, 5298–5308 (2023). https://doi.org/10.1007/s12011-023-03598-z

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