1. The NF-κB transcription factor RelA is required for the tolerogenic function of Foxp3(+) regulatory T cells.
- Author
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Messina N, Fulford T, O'Reilly L, Loh WX, Motyer JM, Ellis D, McLean C, Naeem H, Lin A, Gugasyan R, Slattery RM, Grumont RJ, and Gerondakis S
- Subjects
- Animals, Antibodies blood, Antibodies immunology, Autoimmune Diseases genetics, Autoimmune Diseases immunology, Autoimmune Diseases metabolism, Autoimmune Diseases pathology, Autoimmunity, Biomarkers, Cluster Analysis, Cytokines blood, Cytokines metabolism, Disease Models, Animal, Female, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Gene Expression Profiling, Immunomodulation, Immunophenotyping, Lymphocyte Activation genetics, Lymphocyte Activation immunology, Lymphocyte Count, Male, Mice, Mice, Transgenic, Phenotype, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Transcription Factor RelA genetics, Immune Tolerance genetics, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Transcription Factor RelA metabolism
- Abstract
The properties of CD4(+) regulatory T cell (Treg) subsets are dictated by distinct patterns of gene expression determined by FOXP3 and different combinations of various transcription factors. Here we show the NF-κB transcription factor RelA is constitutively active in naïve and effector Tregs. The conditional inactivation of Rela in murine FOXP3(+) cells induces a rapid onset, multi-focal autoimmune disease that depends on RelA being expressed in conventional T cells. In addition to promoting Treg lineage stability, RelA determines the size of the effector Treg population, a function influenced by the presence or absence of RelA in conventional T cells. These findings showing that RelA controls Treg stability and promotes the competitive fitness of effector Tregs highlight the importance of RelA activity in peripheral Treg induced tolerance., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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