| Literature DB >> 29330161 |
Tobias Wertheimer1,2, Enrico Velardi1, Jennifer Tsai1,3, Kirsten Cooper3, Shiyun Xiao4, Christopher C Kloss5,6, Katja J Ottmüller7, Zeinab Mokhtari7, Christian Brede7, Paul deRoos3, Sinéad Kinsella3, Brisa Palikuqi5, Michael Ginsberg8, Lauren F Young1, Fabiana Kreines1, Sophia R Lieberman1, Amina Lazrak1, Peipei Guo5, Florent Malard1, Odette M Smith1, Yusuke Shono1, Robert R Jenq9, Alan M Hanash9, Daniel J Nolan8, Jason M Butler5, Andreas Beilhack7, Nancy R Manley4, Shahin Rafii5, Jarrod A Dudakov10,11, Marcel R M van den Brink12,9.
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 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.Entities:
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Year: 2018 PMID： 29330161 PMCID： PMC5795617 DOI： 10.1126/sciimmunol.aal2736
Source DB: PubMed Journal: Sci Immunol ISSN： 2470-9468