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Updated: Mar 24, 2026
Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
CXCR4 antagonist AMD3100 ameliorates thyroid damage in autoimmune thyroiditis in NOD.H‑2h⁴ mice
Xin Liu1, Jinyuan Mao1, Cheng Han1
1Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Abstract:
CXC chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor 4 (CXCR4), are upregulated in mice with autoimmune thyroid diseases. However, whether this interaction is involved in the pathophysiology of autoimmune thyroiditis (AIT) remains to be elucidated. In the present study, the effects of the CXCR4 antagonist, AMD3100, in an iodine‑induced autoimmune thyroiditis model were investigated. NOD.H‑2h4 mice were randomly separated into a control, AIT and AIT+AMD3100 groups. The mice were fed with 0.05% sodium iodide water for 8 weeks to induce AIT. The AMD3100‑treated mice were administered with the CXCR4 antagonist at a dose of 10 mg/kg intraperitoneally three times a week during the experimental period. The percentages of CD19+interleukin (IL)10+ B cells and CD4+IL10+ T cells, and the mRNA expression levels of IL10 in the splenocytes were reduced in the AIT group, compared with the control group, however, they increased following AMD3100 treatment, compared with the untreated AIT group. The percentages of CD4+ T cells, CD8+ T cells, CD19+ B cells and CD8+ interferon (IFN)γ+ T cells, and the mRNA expression levels of IFNγ increased in the AIT group, compared with the control group, however, these were reduced in the AMD3100 group, compared with the AIT group. The AMD3100‑treated mice also had lower serum thyroglobulin antibody titers and reduced lymphocytic infiltration in the thyroid, compared with the untreated AIT mice. These results suggested that inhibition of this chemokine axis may offer potential as a therapeutic target for the treatment of AIT.
Insights
Blocking the CXCL12/CXCR4 interaction with AMD3100 reduced autoimmune thyroiditis (AIT) progression in mice. This targeted therapy increased beneficial IL-10 producing cells and decreased harmful IFN-γ producing cells, offering a potential treatment for AIT.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- CXC chemokine ligand 12 (CXCL12) and its receptor CXC chemokine receptor 4 (CXCR4) are implicated in autoimmune thyroid diseases.
- The specific role of the CXCL12/CXCR4 axis in the pathophysiology of autoimmune thyroiditis (AIT) requires further investigation.
Purpose of the Study:
- To investigate the therapeutic effects of the CXCR4 antagonist AMD3100 in a mouse model of iodine-induced autoimmune thyroiditis.
- To elucidate the impact of targeting the CXCL12/CXCR4 axis on immune cell populations and inflammatory markers in AIT.
Main Methods:
- An iodine-induced AIT model was established in NOD.H-2h4 mice.
- Mice were treated with AMD3100 (a CXCR4 antagonist) or a control.
- Immune cell populations (B cells, T cells), cytokine expression (IL-10, IFN-γ), antibody titers, and thyroid lymphocytic infiltration were analyzed.
Main Results:
- AMD3100 treatment increased the percentages of IL-10 producing B cells and T cells, and IL-10 mRNA expression.
- AMD3100 treatment decreased the percentages of CD4+, CD8+ T cells, B cells, IFN-γ producing CD8+ T cells, and IFN-γ mRNA expression.
- AMD3100 administration led to lower serum thyroglobulin antibody titers and reduced lymphocytic infiltration in the thyroid.
Conclusions:
- Inhibition of the CXCL12/CXCR4 chemokine axis using AMD3100 demonstrates therapeutic potential in ameliorating autoimmune thyroiditis.
- Targeting this chemokine interaction may represent a novel strategy for treating AIT by modulating key immune responses.
