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| Item Type: | Article |
|---|---|
| Title: | Central immune tolerance depends on crosstalk between the classical and alternative NF-κB pathways in medullary thymic epithelial cells |
| Creators Name: | Riemann, M., Andreas, N., Fedoseeva, M., Meier, E., Weih, D., Freytag, H., Schmidt-Ullrich, R., Klein, U., Wang, Z.Q. and Weih, F. |
| Abstract: | Medullary thymic epithelial cells (mTECs) contribute to self-tolerance by expressing and presenting peripheral tissue antigens for negative selection of autoreactive T cells and differentiation of natural regulatory T cells. The molecular control of mTEC development remains incompletely understood. We here demonstrate by TEC-specific gene manipulation in mice that the NF-{kappa}B transcription factor subunit RelB, which is activated by the alternative NF-{kappa}B pathway, regulates development of mature mTECs in a dose-dependent manner. Mice with conditional deletion of Relb lacked mature mTECs and developed spontaneous autoimmunity. In addition, the NF-{kappa}B subunits RelA and c-Rel, which are both activated by classical NF-{kappa}B signaling, were jointly required for mTEC differentiation by directly regulating the transcription of Relb. Our data reveal a crosstalk mechanism between classical and alternative NF-{kappa}B pathways that tightly controls the development of mature mTECs to ensure self-tolerance. |
| Keywords: | Autoimmunity, Central Immune Tolerance, Medullary Thymic Epithelial Cells, NF-{kappa}B, Conditional Gene Targeting, Animals, Mice |
| Source: | Journal of Autoimmunity |
| ISSN: | 0896-8411 |
| Publisher: | Elsevier / Academic Press |
| Volume: | 81 |
| Page Range: | 56-67 |
| Date: | July 2017 |
| Official Publication: | https://doi.org/10.1016/j.jaut.2017.03.007 |
| PubMed: | View item in PubMed |
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