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J Immunol. 2017 Aug 15;199(4):1250-1260. doi: 10.4049/jimmunol.1600941. Epub 2017 Jul 12.

Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520.
2
The Francis Crick Institute, London NW1 1AT, United Kingdom.
3
The RNA Institute, University at Albany, State University of New York, Albany, NY 12222.
4
Investigative Medicine Program, Yale University School of Medicine, New Haven, CT 06520.
5
School of Immunity and Infection, Medical Research Council Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, United Kingdom.
6
Section of Experimental Haematology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS2 9JT, United Kingdom.
7
Department of Immunobiology, Yale University, New Haven, CT 06520; and.
8
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520; valerie.horsley@yale.edu.
9
Department of Dermatology, Yale University, New Haven, CT 06520.

Abstract

Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice. Prdm1 is expressed by a subset of mouse TECs, and conditional deletion of Prdm1 in either Keratin 14- or Foxn1-expressing cells in mice resulted in multisymptom autoimmune pathology. Notably, the development of Foxp3+ regulatory T cells occurs normally in the absence of Blimp1. Importantly, nude mice developed anti-nuclear Abs when transplanted with Prdm1 null TECs, but not wild-type TECs, indicating that Prdm1 functions in TECs to regulate autoantibody production. We show that Prdm1 acts independently of Aire, a crucial transcription factor implicated in medullary TEC function. Collectively, our data highlight a previously unrecognized role for Prdm1 in regulating thymic epithelial function.

PMID:
28701508
PMCID:
PMC5544928
DOI:
10.4049/jimmunol.1600941
[Indexed for MEDLINE]
Free PMC Article

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