title: Basal NF-κB controls IL-7 responsiveness of quiescent naïve T cells.
abstract: T cells are essential for immune defenses against pathogens, such that viability of naïve T cells before antigen encounter is critical to preserve a polyclonal repertoire and prevent immunodeficiencies. The viability of naïve T cells before antigen recognition is ensured by IL-7, which drives expression of the prosurvival factor Bcl-2. Quiescent naïve T cells have low basal activity of the transcription factor NF-κB, which was assumed to have no functional consequences. In contrast to this postulate, our data show that basal nuclear NF-κB activity plays an important role in the transcription of IL-7 receptor α-subunit (CD127), enabling responsiveness of naïve T cells to the prosurvival effects of IL-7 and allowing T-cell persistence in vivo. Moreover, we show that this property of basal NF-κB activity is shared by mouse and human naïve T cells. Thus, NF-κB drives a distinct transcriptional program in T cells before antigen encounter by controlling susceptibility to IL-7. Our results reveal an evolutionarily conserved role of NF-κB in T cells before antigenic stimulation and identify a novel molecular pathway that controls T-cell homeostasis.
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Miller
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Mona
authors.initials: M
authors.lastname: Mashayekhi
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Luqiu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742.
authors.forename: Xindong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Monica
authors.initials: M
authors.lastname: Michelotti
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tramontini Gunn
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Powers
authors.affiliation: Laboratory of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Cesar
authors.initials: C
authors.lastname: Evaristo
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and.
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Alegre
authors.affiliation: Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637; and lucianamolinero@gmail.com.
authors.forename: Luciana L
authors.initials: LL
authors.lastname: Molinero
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D002470:Cell Survival; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052002:NF-kappa B p50 Subunit / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D000941:Antigens; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D020395:Receptors, Interleukin-7; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C073701:Nfkb1 protein, mouse; D051550:I-kappa B Kinase
keywords: IKKβ; IkBaDN; Il7r enhancer; STAT5