KLF2 is a rate-limiting transcription factor that can be targeted to enhance regulatory T-cell production.

Pabbisetty SK, Rabacal W, Maseda D, Cendron D, Collins PL, Hoek KL, Parekh VV, Aune TM, Sebzda E
Proc Natl Acad Sci U S A. 2014 111 (26): 9579-84

PMID: 24979767 · PMCID: PMC4084438 · DOI:10.1073/pnas.1323493111

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.

MeSH Terms (11)

Animals Autoimmunity Cell Differentiation Chromatin Immunoprecipitation DNA Primers Flow Cytometry Kruppel-Like Transcription Factors Mice Mice, Inbred C57BL Mice, Transgenic T-Lymphocytes, Regulatory

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