Skip to main content
Article thumbnail
Location of Repository

Comparative genomics reveals key gain-of-function events in Foxp3 during regulatory T cell evolution

By Kristian G Andersen, Jesper K Nissen and Alexander G Betz

Abstract

The immune system has the ability to suppress undesirable responses, such as those against commensal bacteria, food and paternal antigens in placenta pregnancy. The lineage-specific transcription factor Foxp3 orchestrates the development and function of regulatory T cells underlying this immunological tolerance. Despite the crucial role of Foxp3 in supporting immune homeostasis, little is known about its origin, evolution and species conservation. We explore these questions using comparative genomics, structural modeling and functional analyses. Our data reveal that key gain-of-function events occurred during the evolution of Foxp3 in higher vertebrates. We identify key conserved residues in its forkhead domain and show a detailed analysis of the N-terminal region of Foxp3, which is only conserved in mammals. These components are under purifying selection, and our mutational analyses demonstrate that they are essential for Foxp3 function. Our study points to critical functional adaptations in immune tolerance among higher vertebrates, and suggests that Foxp3-mediated transcriptional mechanisms emerged during mammalian evolution as a step-wise gain of functional domains that enabled Foxp3 to interact with a multitude of interaction partners

Topics: Regulatory T Cell, Foxp3, Evolution of Immune System, Lineage commitment, Comparative genomics, Immunologic diseases. Allergy, RC581-607
Publisher: Frontiers Media S.A.
Year: 2012
DOI identifier: 10.3389/fimmu.2012.00113
OAI identifier: oai:doaj.org/article:5cf17ee588714866a5a0a679da12b003
Journal:
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • https://doaj.org/toc/1664-3224 (external link)
  • http://journal.frontiersin.org... (external link)
  • https://doaj.org/article/5cf17... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.