Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 4, Pages 1250-1260Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1600941
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Funding
- Pew Scholar in Biomedical Research Award
- Medical Research Council Programme
- Cancer Research UK Senior Clinical Fellowship [C7845/A10066]
- National Institutes of Health [R37AI066232, AR060295]
- Howard Hughes Medical Institute
- Connecticut Department of Public Health [12SCBYALE01]
- MRC [MR/N000919/1] Funding Source: UKRI
- Medical Research Council [MR/N000919/1] Funding Source: researchfish
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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.
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