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Title of the item:

The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.

Title :
The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.
Authors :
Hikosaka Y; Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
Nitta T
Ohigashi I
Yano K
Ishimaru N
Hayashi Y
Matsumoto M
Matsuo K
Penninger JM
Takayanagi H
Yokota Y
Yamada H
Yoshikai Y
Inoue J
Akiyama T
Takahama Y
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Source :
Immunity [Immunity] 2008 Sep 19; Vol. 29 (3), pp. 438-50.
Publication Type :
Journal Article; Research Support, Non-U.S. Gov't
Language :
Imprint Name(s) :
Publication: Cambridge, MA : Cell Press
Original Publication: Cambridge, Mass. : Cell Press, c1994-
MeSH Terms :
Epithelial Cells/*immunology
RANK Ligand/*metabolism
Receptor Activator of Nuclear Factor-kappa B/*metabolism
TNF-Related Apoptosis-Inducing Ligand/*metabolism
Thymus Gland/*immunology
Transcription Factors/*metabolism
Animals ; Autoimmunity ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Mice ; Osteoprotegerin/metabolism ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Self Tolerance ; T-Lymphocytes/cytology ; T-Lymphocytes/metabolism ; Thymus Gland/cytology ; Thymus Gland/metabolism
Substance Nomenclature :
0 (APECED protein)
0 (Osteoprotegerin)
0 (RANK Ligand)
0 (Receptor Activator of Nuclear Factor-kappa B)
0 (Receptors, Antigen, T-Cell)
0 (TNF-Related Apoptosis-Inducing Ligand)
0 (Transcription Factors)
Entry Date(s) :
Date Created: 20080919 Date Completed: 20081016 Latest Revision: 20090608
Update Code :
Academic Journal
The thymic medulla provides a microenvironment where medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic medulla formation via a previously unknown mechanism. Here we show that the cytokine RANK ligand (RANKL) was produced by positively selected thymocytes and regulated the cellularity of mTEC by interacting with RANK and osteoprotegerin. Forced expression of RANKL restored thymic medulla in mice lacking positive selection, whereas RANKL perturbation impaired medulla formation. These results indicate that RANKL produced by positively selected thymocytes is responsible for fostering thymic medulla formation, thereby establishing central tolerance.
Comment in: Immunity. 2008 Sep 19;29(3):386-8. (PMID: 18799147)

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