title: KLF2 is a rate-limiting transcription factor that can be targeted to enhance regulatory T-cell production.
abstract: Regulatory T cells (Tregs) are a specialized subset of CD4(+) T cells that maintain self-tolerance by functionally suppressing autoreactive lymphocytes. The Treg compartment is composed of thymus-derived Tregs (tTregs) and peripheral Tregs (pTregs) that are generated in secondary lymphoid organs after exposure to antigen and specific cytokines, such as TGF-β. With regard to this latter lineage, pTregs [and their ex vivo generated counterparts, induced Tregs (iTregs)] offer particular therapeutic potential because these cells can be raised against specific antigens to limit autoimmunity. We now report that transcription factor Krüppel-like factor 2 (KLF2) is necessary for the generation of iTregs but not tTregs. Moreover, drugs that limit KLF2 proteolysis during T-cell activation enhance iTreg development. To the authors' knowledge, this study identifies the first transcription factor to distinguish between i/pTreg and tTreg ontogeny and demonstrates that KLF2 is a therapeutic target for the production of regulatory T cells.
authors: Departments of Pathology, Microbiology, and Immunology, and.
authors: Sudheer K
authors: SK
authors: Pabbisetty
authors: Departments of Pathology, Microbiology, and Immunology, and.
authors: Whitney
authors: W
authors: Rabacal
authors: Departments of Pathology, Microbiology, and Immunology, and.
authors: Damian
authors: D
authors: Maseda
authors: Departments of Pathology, Microbiology, and Immunology, and.
authors: Delphine
authors: D
authors: Cendron
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors: Patrick L
authors: PL
authors: Collins
authors: Departments of Pathology, Microbiology, and Immunology, and.
authors: Kristen L
authors: KL
authors: Hoek
authors: Departments of Pathology, Microbiology, and Immunology, and.
authors: Vrajesh V
authors: VV
authors: Parekh
authors: Departments of Pathology, Microbiology, and Immunology, andMedicine, Vanderbilt University School of Medicine, Nashville, TN 37232; and.
authors: Thomas M
authors: TM
authors: Aune
authors: Departments of Pathology, Microbiology, and Immunology, and eric.sebzda@vanderbilt.edu.
authors: Eric
authors: E
authors: Sebzda
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D051741:Kruppel-Like Transcription Factors / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D017931:DNA Primers; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors