ArticleJournal of immunology (Baltimore, Md. : 1950)2011
IFN-α mediates the development of autoimmunity both by direct tissue toxicity and through immune cell recruitment mechanisms.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Efficacy of Xiaoyao-san preparations in treating Hashimoto's thyroiditis: a meta-analysis and systematic review.Frontiers in pharmacology · 2025Pooled it
- Patterns of interferon-alpha-induced thyroid dysfunction vary with ethnicity, sex, smoking status, and pretreatment thyrotropin in an international cohort of patients treated for hepatitis C.Thyroid : official journal of the American Thyroid Association · 2013Trial
- Disease and Treatment-Specific Complications of Behçet Syndrome.Current rheumatology reports · 2024Review
- HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease.The Journal of clinical endocrinology and metabolism · 2021Article
- Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs.BMC genomics · 2020Article
- Hepatitis C Virus Infection of Human Thyrocytes: Metabolic, Hormonal, and Immunological Implications.The Journal of clinical endocrinology and metabolism · 2020Article
- Toll-Like Receptors-2 and -4 in Graves' Disease-Key Players or Bystanders?International journal of molecular sciences · 2019Article
- Epigenetic modulation of β cells by interferon-α via PNPT1/mir-26a/TET2 triggers autoimmune diabetes.JCI insight · 2019Article
- Interferon alpha: The key trigger of type 1 diabetes.Journal of autoimmunity · 2018Review
- Interferon-α Triggers Autoimmune Thyroid Diseases via Lysosomal-Dependent Degradation of Thyroglobulin.The Journal of clinical endocrinology and metabolism · 2018Article
- Risk factors and disease mechanisms in myositis.Nature reviews. Rheumatology · 2018Review
- The frequency of hypothyroidism and its relationship with HCV positivity in patients with thalassemia major in southern Iran.Acta bio-medica : Atenei Parmensis · 2018Article
- PINTnet: construction of condition-specific pathway interaction network by computing shortest paths on weighted PPI.BMC systems biology · 2017Article
- Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells.The Journal of clinical endocrinology and metabolism · 2017Article
- Autoimmune Thyroiditis and Myasthenia Gravis.Frontiers in endocrinology · 2017Review
- Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases.Frontiers in immunology · 2017Review
- Type I IFN family members: similarity, differences and interaction.Cytokine & growth factor reviews · 2015Review
- Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells.International journal of endocrinology · 2015Article
- Diabetes and Hepatitis C: A Two-Way Association.Frontiers in endocrinology · 2015Review
- Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
IFN-α is known to play a key role in autoimmunity, but the mechanisms are uncertain. Although the induction of autoimmunity by IFN-α is consistent with primarily immunomodulatory effects, the high frequency of nonautoimmune inflammation suggests other mechanisms. We used thyroiditis as a model to dissect these possibilities. IFN-α treatment of cultured thyrocytes increased expression of thyroid differentiation markers, thyroglobulin, thyroid-stimulating hormone receptor, thyroid peroxidase, and sodium iodide transporter. RNAseq analysis demonstrated that pathways of Ag presentation, pattern recognition receptors, and cytokines/chemokines were also stimulated. These changes were associated with markedly increased nonapoptotic thyroid cell death, suggesting direct toxicity. To corroborate these in vitro findings, we created transgenic mice with thyroid-specific overexpression of IFN-α under control of the thyroglobulin promoter. Transgenic mice developed marked inflammatory thyroid destruction associated with immune cell infiltration of thyroid and surrounding tissues leading to profound hypothyroidism, findings consistent with our in vitro results. In addition, transgenic mice thyroids showed upregulation of pathways similar to those observed in cultured thyrocytes. In particular, expression of granzyme B, CXCL10, a subset of the tripartite motif-containing family, and other genes involved in recruitment of bystander cytotoxic immune responses were increased. Pathways associated with apoptosis and autophagy were not induced. Taken together, our data demonstrate that the induction of tissue inflammation and autoimmunity by IFN-α involves direct tissue toxic effects as well as provocation of destructive bystander immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.