Signal transducer and activator of transcription (Stat)-6-dependent, but not Sat4-dependent, immunity is required for the development of autoimmunity in Graves' hyperthyroidism

Kimberly J. Land, Jennifer S. Moll, Mark Kaplan, Gattadahalli Seetharamaiah

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The role of T helper (Th) cells in experimental models of Graves' hyperthyroidism is still somewhat controversial. To further investigate the role of Th1- and Th2-dependent immunity during the development of Graves' hyperthyroidism, we tested mice with targeted deletion of signal transducer and activator of transcription-4 (Stat4) or Stat6 genes that, respectively, have impaired Th1 and Th2 immunity. We immunized wild-type BALB/c, Stat4 -/-, or Stat6-/- mice with human embryonic kidney cells (293 cells) expressing the extracellular domain of human TSH receptor (293-TBP cells). Fifty percent of wild-type BALB/c and Stat4-/- mice developed Graves' hyperthyroidism with elevated serum T4 levels and thyroid stimulatory antibodies. In contrast, Stat6-/- mice resisted development of the disease. Stat4-/- mice exhibited a dominant Th2 immune response characterized by the production of IL-4 and IgG1 anti-TSH receptor antibodies. However, Stat6-/- mice displayed a strong Th1 immune response characterized by the production of interferon-γ and IgG2a antibodies. Hyperthyroid mice showed enlargement of thyroid glands with hypertrophy and decreased amounts of colloid material, all characteristics of Graves' disease. These data demonstrate that in this model, Stat6-dependent Th2 immunity is critical for the development of Graves' hyperthyroidism.

Original languageEnglish
Pages (from-to)3724-3730
Number of pages7
JournalEndocrinology
Volume145
Issue number8
DOIs
StatePublished - Aug 2004

Fingerprint

STAT6 Transcription Factor
Hyperthyroidism
Autoimmunity
STAT4 Transcription Factor
Immunity
Thyroid Gland
Thyrotropin Receptors
Antibodies
Graves Disease
Colloids
Helper-Inducer T-Lymphocytes
Interleukin-4
Interferons
Hypertrophy
Theoretical Models
Immunoglobulin G
Kidney

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Signal transducer and activator of transcription (Stat)-6-dependent, but not Sat4-dependent, immunity is required for the development of autoimmunity in Graves' hyperthyroidism",
abstract = "The role of T helper (Th) cells in experimental models of Graves' hyperthyroidism is still somewhat controversial. To further investigate the role of Th1- and Th2-dependent immunity during the development of Graves' hyperthyroidism, we tested mice with targeted deletion of signal transducer and activator of transcription-4 (Stat4) or Stat6 genes that, respectively, have impaired Th1 and Th2 immunity. We immunized wild-type BALB/c, Stat4 -/-, or Stat6-/- mice with human embryonic kidney cells (293 cells) expressing the extracellular domain of human TSH receptor (293-TBP cells). Fifty percent of wild-type BALB/c and Stat4-/- mice developed Graves' hyperthyroidism with elevated serum T4 levels and thyroid stimulatory antibodies. In contrast, Stat6-/- mice resisted development of the disease. Stat4-/- mice exhibited a dominant Th2 immune response characterized by the production of IL-4 and IgG1 anti-TSH receptor antibodies. However, Stat6-/- mice displayed a strong Th1 immune response characterized by the production of interferon-γ and IgG2a antibodies. Hyperthyroid mice showed enlargement of thyroid glands with hypertrophy and decreased amounts of colloid material, all characteristics of Graves' disease. These data demonstrate that in this model, Stat6-dependent Th2 immunity is critical for the development of Graves' hyperthyroidism.",
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T1 - Signal transducer and activator of transcription (Stat)-6-dependent, but not Sat4-dependent, immunity is required for the development of autoimmunity in Graves' hyperthyroidism

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AU - Kaplan, Mark

AU - Seetharamaiah, Gattadahalli

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