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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.

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


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.

[Indexed for MEDLINE]
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