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Constructing the optimal experimental autoimmune thyroiditis mouse model using porcine thyroglobulin.

Ke Liu1, Pei Zhang2, Zi-Shan Jin3

  • 1Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Frontiers in Immunology
|September 5, 2025
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Summary
This summary is machine-generated.

Developing an optimal animal model for autoimmune thyroiditis (AIT) involved comparing immunization strategies in NOD/LtJ mice. High-dose antigen with frequent injections effectively induced AIT, paving the way for AIT pathogenesis and therapy research.

Keywords:
NOD/LtJ miceanimal model constructionautoimmune thyroiditisexperimental autoimmune thyroiditismolecular mechanism

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Area of Science:

  • Immunology
  • Endocrinology
  • Animal Modeling

Background:

  • Autoimmune thyroiditis (AIT) is a growing concern with no standardized animal model.
  • Understanding AIT pathogenesis and developing targeted immunotherapies require a reliable model.

Purpose of the Study:

  • To systematically compare different immunization conditions for developing an optimal NOD/LtJ mouse model of AIT.
  • To elucidate the pathological and immunological effects of varying antigen doses, frequencies, and administration routes.

Main Methods:

  • NOD/LtJ mice were immunized subcutaneously (SC) or intravenously (IV) with porcine thyroglobulin (pTg) under varied doses and frequencies.
  • Thyroid histopathology, serum autoantibodies (TPO-Ab, TG-Ab), cytokines, T helper 17 (Th17)/regulatory T (Treg) cells, and inflammasome components (NLRP3, Caspase-1) were analyzed.

Main Results:

  • High-dose (200 μg) pTg with three immunizations induced severe thyroiditis, follicular destruction, and elevated autoantibodies in both SC and IV groups.
  • This protocol activated Th1/Th17 cytokines and increased Treg cells, with enhanced thyroid NLRP3 inflammasome activation.
  • IV injection showed superior antibody production and inflammasome activation, while SC injection led to more pronounced histological inflammation.

Conclusions:

  • A combination of high-dose antigen (200 μg pTg) and three immunizations, particularly via tail vein injection, effectively models AIT in NOD/LtJ mice.
  • This optimized protocol enhances experimental efficiency and reproducibility for AIT research.
  • The findings provide a robust foundation for investigating AIT pathogenesis and evaluating novel immunotherapies.