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Polymorphic estroge...
Polymorphic estrogen receptor binding site causes Cd2-dependent sex bias in the susceptibility to autoimmune diseases
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- Lahore, GF (author)
- Karolinska Institute, Solna, Sweden
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Forster, M (author)
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- Johannesson, M (author)
- Karolinska Institutet
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- Sabatier, P (author)
- Karolinska Institutet
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- Lonnblom, E (author)
- Karolinska Institutet
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- Aoun, M (author)
- Karolinska Institutet
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- He, YB (author)
- Karolinska Institutet
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- Nandakumar, Kutty Selva, 1965- (author)
- Karolinska Institute, Solna, Sweden; Southern Medical University, Guangzhou, China
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- Zubarev, RA (author)
- Karolinska Institutet
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- Holmdahl, R (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2021-09-22
- 2021
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 5565-
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Abstract
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- Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors probably controls the sex discrepancy in the immune response, but the underlying mechanisms are unclear. Here we positionally identify a polymorphic estrogen receptor binding site that regulates Cd2 expression, leading to female-specific differences in T cell-dependent mouse models of autoimmunity. Female mice with reduced Cd2 expression have impaired autoreactive T cell responses. T cells lacking Cd2 costimulation upregulate inhibitory Lag-3. These findings help explain sexual dimorphism in human autoimmunity, as we find that CD2 polymorphisms are associated with rheumatoid arthritis and 17-β-estradiol-regulation of CD2 is conserved in human T cells. Hormonal regulation of CD2 might have implications for CD2-targeted therapy, as anti-Cd2 treatment more potently affects T cells in female mice. These results demonstrate the relevance of sex-genotype interactions, providing strong evidence for CD2 as a sex-sensitive predisposing factor in autoimmunity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lahore, GF
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Forster, M
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Johannesson, M
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Sabatier, P
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Lonnblom, E
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Aoun, M
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show more...
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He, YB
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Nandakumar, Kutt ...
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Zubarev, RA
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Holmdahl, R
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature communica ...
- By the university
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Karolinska Institutet
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Halmstad University