The transcription factor NR4A1 is essential for the development of a novel macrophage subset in the thymus

Sci Rep. 2015 Jun 19:5:10055. doi: 10.1038/srep10055.

Abstract

Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue macrophages derive from one of a small number of progenitor programs, the transcriptional requirements for site-specific macrophage subset development are more complex. We have identified a new tissue macrophage subset in the thymus and have discovered that its development is dependent on transcription factor NR4A1. Functionally, we find that NR4A1-dependent macrophages are critically important for clearance of apoptotic thymocytes. These macrophages are largely reduced or absent in mice lacking NR4A1, and Nr4a1-deficient mice have impaired thymocyte engulfment and clearance. Thus, NR4A1 functions as a master transcription factor for the development of this novel thymus-specific macrophage subset.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / immunology*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mice
  • Mice, Knockout
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / immunology*
  • Thymocytes / cytology
  • Thymocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1