Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration Academic Article uri icon

Overview

MeSH Major

  • Gene Expression Regulation, Leukemic
  • Intracellular Signaling Peptides and Proteins
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Models, Statistical
  • Phospholipase C gamma
  • Protein-Tyrosine Kinases
  • Receptors, Antigen, B-Cell
  • Signal Transduction

abstract

  • Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance, and regeneration, and its downstream targets such as Dll4, a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity.

authors

publication date

  • January 12, 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5795617

Digital Object Identifier (DOI)

  • 10.1126/sciimmunol.aal2736

PubMed ID

  • 29330161

Additional Document Info

volume

  • 3

number

  • 19