Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity

  • Roberts N
  • Adams B
  • McCarthy N
  • et al.
20Citations
Citations of this article
49Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Roberts, N. A., Adams, B. D., McCarthy, N. I., Tooze, R. M., Parnell, S. M., Anderson, G., … Horsley, V. (2017). Prdm1 Regulates Thymic Epithelial Function To Prevent Autoimmunity. The Journal of Immunology, 199(4), 1250–1260. https://doi.org/10.4049/jimmunol.1600941

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free