Author
Listed:
- Meng-Lei Zhu
(School of Medicine, University of North Carolina at Chapel Hill
School of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)
- Pearl Bakhru
(School of Medicine, University of North Carolina at Chapel Hill
School of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)
- Bridget Conley
(School of Medicine, University of North Carolina at Chapel Hill
School of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)
- Jennifer S. Nelson
(School of Medicine, University of North Carolina at Chapel Hill)
- Meghan Free
(School of Medicine, University of North Carolina at Chapel Hill)
- Aaron Martin
(School of Medicine, University of North Carolina at Chapel Hill)
- Joshua Starmer
(University of North Carolina at Chapel Hill)
- Elizabeth M. Wilson
(School of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
School of Medicine, University of North Carolina at Chapel Hill)
- Maureen A. Su
(School of Medicine, University of North Carolina at Chapel Hill
School of Medicine, University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)
Abstract
Male gender is protective against multiple sclerosis and other T-cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well understood. Autoimmune regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared with females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity.
Suggested Citation
Meng-Lei Zhu & Pearl Bakhru & Bridget Conley & Jennifer S. Nelson & Meghan Free & Aaron Martin & Joshua Starmer & Elizabeth M. Wilson & Maureen A. Su, 2016.
"Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator,"
Nature Communications, Nature, vol. 7(1), pages 1-14, September.
Handle:
RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11350
DOI: 10.1038/ncomms11350
Download full text from publisher
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- Jean Lee & Leonid A. Yurkovetskiy & Derek Reiman & Lara Frommer & Zoe Strong & Anthony Chang & George J. Kahaly & Aly A. Khan & Alexander V. Chervonsky, 2024.
"Androgens contribute to sex bias of autoimmunity in mice by T cell-intrinsic regulation of Ptpn22 phosphatase expression,"
Nature Communications, Nature, vol. 15(1), pages 1-19, December.
- Amina Zahaf & Abdelmoumen Kassoussi & Tom Hutteau-Hamel & Amine Mellouk & Corentine Marie & Lida Zoupi & Foteini Tsouki & Claudia Mattern & Pierre Bobé & Michael Schumacher & Anna Williams & Carlos Pa, 2023.
"Androgens show sex-dependent differences in myelination in immune and non-immune murine models of CNS demyelination,"
Nature Communications, Nature, vol. 14(1), pages 1-21, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11350. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.