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Ovarian autoimmune disease: clinical concepts and animal models

Cellular & Molecular Immunology volume 11, pages 510–521 (2014)Cite this article

Abstract

The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models.

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Acknowledgements

The authors thank the many members of their labs who have contributed valuably to the work in this article through discussion and interaction. We are grateful to Matahb Fakhari for technical work with ovarian immunohistochemistry. The Aire-deficient mice were a generous donation from the laboratory of Christoph Benoist and Diane Mathis at Harvard Medical School. This work was supported by NIH grants R21HD062879 and R01HD045611 to MGP.

Author information

Author notes

  1. Brian K Petroff

    Present address: Present address: Department of Pathobiology and Diagnostic Investigation, Michigan State University College of Veterinary Medicine, East Lansing, MI, USA

  2. Dr. MG Petroff, Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. E-mail: mpetroff@kumc.edu

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA

    Bryce D Warren, William K Kinsey, Susmita Jasti & Margaret G Petroff

  2. Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA

    Lynda K McGinnis & Lane K Christenson

  3. and Division of Rheumatology, Department of Pediatrics, Research Center for Immunity and Immunotherapies, Children's Hospital and Regional Medical Center, University of Washington, Seattle, WA, USA

    Anne M Stevens

  4. Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA

    Brian K Petroff

Authors
  1. Bryce D Warren
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  2. William K Kinsey
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  3. Lynda K McGinnis
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  4. Lane K Christenson
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  5. Susmita Jasti
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  6. Anne M Stevens
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  7. Brian K Petroff
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  8. Margaret G Petroff
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Warren, B., Kinsey, W., McGinnis, L. et al. Ovarian autoimmune disease: clinical concepts and animal models. Cell Mol Immunol 11, 510–521 (2014). https://doi.org/10.1038/cmi.2014.97

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  • DOI: https://doi.org/10.1038/cmi.2014.97

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