Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration Journal Article

Authors: Wertheimer, T.; Velardi, E.; Tsai, J.; Cooper, K.; Xiao, S.; Kloss, C. C.; Ottmuller, K. J.; Mokhtari, Z.; Brede, C.; deRoos, P.; Kinsella, S.; Palikuqi, B.; Ginsberg, M.; Young, L. F.; Kreines, F.; Lieberman, S. R.; Lazrak, A.; Guo, P.; Malard, F.; Smith, O. M.; Shono, Y.; Jenq, R. R.; Hanash, A. M.; Nolan, D. J.; Butler, J. M.; Beilhack, A.; Manley, N. R.; Rafii, S.; Dudakov, J. A.; van den Brink, M. R. M.
Article Title: Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration
Abstract: 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 Foxnl, 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.
Keywords: self-renewal; differentiation; epithelial-cells; hematopoietic stem-cells; bone-marrow-transplantation; vascular niche; delta-like 4; adult thymus; angiocrine signals; foxn1
Journal Title: Science Immunology
Volume: 3
Issue: 19
ISSN: 2470-9468
Publisher: Amer Assoc Advancement Science  
Date Published: 2018-01-12
Start Page: eaal2736
Language: English
ACCESSION: WOS:000434330300001
DOI: 10.1126/sciimmunol.aal2736
PMCID: PMC5795617
PUBMED: 29330161
Notes: Article -- UNSP eaa12736 -- Source: Wos
Citation Impact
MSK Authors
  1. Alan M Hanash
    106 Hanash
  2. Robert R Jenq
    107 Jenq
  3. Jennifer Tsai
    48 Tsai
  4. Yusuke Shono
    38 Shono
  5. Enrico Velardi
    44 Velardi
  6. Odette Marsinay Smith
    98 Smith
  7. Lauren Young
    39 Young
  8. Fabiana Maria Kreines
    14 Kreines
  9. Christopher Carl Kloss
    11 Kloss
  10. Florent Malard
    5 Malard
  11. Amina Lazrak
    18 Lazrak