title: The NF-κB transcription factor RelA is required for the tolerogenic function of Foxp3(+) regulatory T cells.
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.
authors.affiliation: Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Messina
authors.affiliation: Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fulford
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Lorraine
authors.initials: L
authors.lastname: O'Reilly
authors.affiliation: Department of Immunology, Monash University Central Clinical School, Prahran, Victoria 3004, Australia.
authors.forename: Wen Xian
authors.initials: WX
authors.lastname: Loh
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Motyer
authors.affiliation: Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Darcy
authors.initials: D
authors.lastname: Ellis
authors.affiliation: Department of Anatomical Pathology, The Alfred Hospital, Prahran, Victoria 3004, Australia.
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.affiliation: Monash Bioinformatics Platform, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Haroon
authors.initials: H
authors.lastname: Naeem
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G, Parkville, Victoria 3052, Australia.
authors.forename: Ann
authors.initials: A
authors.lastname: Lin
authors.affiliation: The Burnet Institute, Prahran, Victoria 3004, Australia.
authors.forename: Raffi
authors.initials: R
authors.lastname: Gugasyan
authors.affiliation: Department of Immunology, Monash University Central Clinical School, Prahran, Victoria 3004, Australia.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Slattery
authors.affiliation: Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Raelene J
authors.initials: RJ
authors.lastname: Grumont
authors.affiliation: Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: steven.gerondakis@monash.edu.
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity; D015415:Biomarkers; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D007108:Immune Tolerance / Q000235:genetics; D056747:Immunomodulation; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015415:Biomarkers; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D051996:Transcription Factor RelA
keywords: Autoimmune disease; Conditional gene targeting; Nuclear factor of kappaB; Regulatory T cells; RelA