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TRAF3 enforces the requirement for T cell cross-talk in thymic medullary epithelial development
Journal article   Open access   Peer reviewed

TRAF3 enforces the requirement for T cell cross-talk in thymic medullary epithelial development

S. Rhiannon Jenkinson, Joy A Williams, Hyein Jeon, Jingjing Zhang, Takeshi Nitta, Izumi Ohigashi, Michael Kruhlak, Saulius Zuklys, Susan Sharrow, Anthony Adams, …
Proceedings of the National Academy of Sciences - PNAS, Vol.110(52), pp.21107-21112
12/24/2013
DOI: 10.1073/pnas.1314859111
PMCID: PMC3876204
PMID: 24324158
url
https://doi.org/10.1073/pnas.1314859111View
Published (Version of record) Open Access

Abstract

Induction of tolerance to self-antigens in developing T cells depends on medullary thymic epithelial cells (mTECs), whose development, in turn, requires signals from mature single-positive (SP) thymocytes, a bidirectional interdependence termed cross-talk. We have probed the mechanism that underlies this requirement for cross-talk. Strikingly, selective deletion in thymic epithelial cells of TNF receptor-associated factor 3 (TRAF3), an inhibitor of nonclassical NF-kB signaling, resulted in development of normal numbers of fully mature mTECs in the complete absence of SP thymocytes. Thus, mTEC development can, in fact, occur in the absence of cross-talk with SP thymocytes, and the role of thymocytes is in overcoming TRAF3-imposed inhibition. We conclude that TRAF3 plays a central role in regulation of mTECs by imposing requirements for T cell cross-talk.
Biological Sciences

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