New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland
| Autor: | Timothy Kayes, Edward F. Downey, Helen Braley-Mullen, James S. Cole, Lucas T. Woods, Cole Bredehoeft, Jean M. Camden, Gary A. Weisman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Regulatory T cell T-Lymphocytes TEC education Immunology Thyroid Gland Salivary Gland Diseases Article Autoimmune Diseases Interferon-gamma Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine CD28 Antigens Hypothyroidism Internal medicine Animals Immunology and Allergy Medicine CD40 Antigens Cells Cultured Hyperplasia CD40 Salivary gland biology business.industry CD28 Epithelial Cells hemic and immune systems medicine.disease Thyroid Diseases Epithelium Mice Inbred C57BL Disease Models Animal Thyroxine 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Sodium iodide biology.protein business tissues Iodine 030215 immunology |
| Zdroj: | The Journal of Immunology. 197:2119-2130 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Sixty to seventy percent of IFN-γ−/− NOD.H-2h4 mice given sodium iodide (NaI)–supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28−/− mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28−/−IFN-γ−/− mice develop severe TEC H/P, and 2–3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4+ T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40−/−IFN-γ−/−CD28−/− mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ−/−CD28−/− mice is a result of reduced regulatory T cell (Treg) numbers, as CD28−/− mice have significantly fewer Tregs, and transfer of CD28+ Tregs inhibits TEC H/P. Essentially all female IFN-γ−/−CD28−/− NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems. |
| Databáze: | OpenAIRE |
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