Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity

Natalie A. Roberts, Brian D. Adams, Nicholas I. McCarthy, Reuben M. Tooze, Sonia M. Parnell, Graham Anderson, Susan M. Kaech, Valerie Horsley

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1250-1260
Number of pages11
JournalJournal of Immunology
Issue number4
Publication statusPublished - 7 Aug 2017


  • Animals
  • Antibodies, Antinuclear
  • Autoantibodies
  • Autoimmunity
  • Epithelial Cells
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Keratin-14
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Positive Regulatory Domain I-Binding Factor 1
  • T-Lymphocytes
  • T-Lymphocytes, Regulatory
  • Thymus Gland
  • Transcription Factors
  • Journal Article


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