Journal article : Review
The contribution of thymic tolerance to central nervous system autoimmunity
- Abstract:
- Autoimmune diseases of the central nervous system (CNS) are associated with high levels of morbidity and economic cost. Research efforts have previously focused on the contribution of the peripheral adaptive and innate immune systems to CNS autoimmunity. However, a failure of thymic negative selection is a necessary step in CNS-reactive T cells escaping into the periphery. Even with defective thymic or peripheral tolerance, the development of CNS inflammation is rare. The reasons underlying this are currently poorly understood. In this review, we examine evidence implicating thymic selection in the pathogenesis of CNS autoimmunity. Animal models suggest that thymic negative selection is an important factor in determining susceptibility to and severity of CNS inflammation. There are indirect clinical data that suggest thymic function is also important in human CNS autoimmune diseases. Specifically, the association between thymoma and paraneoplastic encephalitis and changes in T cell receptor excision circles in multiple sclerosis implicate thymic tolerance in these diseases. We identify potential associations between CNS autoimmunity susceptibility factors and thymic tolerance. The therapeutic manipulation of thymopoiesis has the potential to open up new treatment modalities, but a better understanding of thymic tolerance in CNS autoimmunity is required before this can be realised.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.9MB, Terms of use)
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- Publisher copy:
- 10.1007/s00281-020-00822-z
Authors
- Publisher:
- Springer
- Journal:
- Seminars in Immunopathology More from this journal
- Volume:
- 43
- Issue:
- 1
- Pages:
- 135–157
- Publication date:
- 2020-10-27
- Acceptance date:
- 2020-10-09
- DOI:
- EISSN:
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1863-2300
- ISSN:
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1863-2297
- Language:
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English
- Keywords:
- Subtype:
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Review
- Pubs id:
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1140069
- Local pid:
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pubs:1140069
- Deposit date:
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2020-10-28
Terms of use
- Copyright holder:
- Alberti and Handel.
- Copyright date:
- 2020
- Rights statement:
- ©2020 The Author(s).
- Notes:
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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