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PMID: 27776542 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Extensive RNA editing and splicing increase immune self-representation diversity in medullary thymic epithelial cells.

Genome biology ·Vol. 17 ·No. 1 ·2016-00-24 ·Pages 219

Danan-Gotthold M, Guyon C, Giraud M, Levanon EY, Abramson J

Abstract

In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells that have a unique capacity to express, and subsequently present, a large fraction of body antigens. While the scope of promiscuously expressed genes by medullary thymic epithelial cells is well-established, relatively little is known about the expression of variants that are generated by co-transcriptional and post-transcriptional processes. Our study reveals that in comparison to other cell types, medullary thymic epithelial cells display significantly higher levels of alternative splicing, as well as A-to-I and C-to-U RNA editing, which thereby further expand the diversity of their self-antigen repertoire. Interestingly, Aire, the key mediator of promiscuous gene expression in these cells, plays a limited role in the regulation of these transcriptional processes. Our results highlight RNA processing as another layer by which the immune system assures a comprehensive self-representation in the thymus which is required for the establishment of self-tolerance and prevention of autoimmunity.

Keywords
Alternative splicing Medullary thymic epithelial cells (mTECs) RNA editing RNA sequencing Self-tolerance Thymus
MeSH Terms
Alternative Splicing/genetics,immunology Animals Autoantigens/genetics,immunology Cell Differentiation/immunology Epithelial Cells/immunology Gene Expression Regulation/immunology Humans Mice RNA Editing/genetics,immunology Self Tolerance/immunology T-Lymphocytes/immunology Thymus Gland/immunology Transcription Factors/genetics
Chemicals
Autoantigens Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Danan-Gotthold Miri ORCID
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
Guyon Clotilde
Department of Infection Immunity and Inflammation, Cochin Institute, Paris, France.
Giraud Matthieu
Department of Infection Immunity and Inflammation, Cochin Institute, Paris, France.
Levanon Erez Y
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel. [email protected].
Abramson Jakub
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. [email protected].
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Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/s13059-016-1079-9
Email
[email protected]
[email protected]
Published
2016-00-24
Epub
2016-00-24
Pages
219
Language
English
Region
England
NLM ID
100960660
PMCID
PMC5078920
Subset
IM
Grants
European Research Council · 311257 · International
External Links
PubMed source DOI: 10.1186/s13059-016-1079-9 PMC Full Text View journal details
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