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[Untitled]
- Source :
- Journal of Clinical Investigation, Journal of Clinical Investigation, American Society for Clinical Investigation, 2016, 126 (4), pp.1525-37. ⟨10.1172/JCI81894⟩, Journal of Clinical Investigation, 2016, 126 (4), pp.1525-37. ⟨10.1172/JCI81894⟩
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Abstract
- International audience; Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue-specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor α-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
medicine.drug_class
Population
Estrogen receptor
Biology
MESH: Estrogens
03 medical and health sciences
MESH: DNA Methylation
0302 clinical medicine
MESH: Autoimmune Diseases
MESH: Child
Internal medicine
Male castration
medicine
MESH: Animals
MESH: Mice, Inbred C3H
MESH: CpG Islands
education
MESH: Mice
MESH: Estrogen Receptor alpha
MESH: Adolescent
education.field_of_study
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
MESH: Humans
MESH: Middle Aged
MESH: Child, Preschool
MESH: Adult
MESH: Thymus Gland
MESH: Transcription Factors
General Medicine
Autoimmune regulator
MESH: Gene Expression Regulation
MESH: Infant
MESH: Male
Thymic Tissue
030104 developmental biology
Endocrinology
Estrogen
Central tolerance
MESH: Female
Estrogen receptor alpha
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
MESH: Sex Characteristics
MESH: Cells, Cultured
030215 immunology
Subjects
Details
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....0481457f0810b7665be34948d79e2fe0