Stable inhibitory activity of regulatory T cells requires the transcription factor Helios.

Autor: Kim HJ; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA., Barnitz RA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA., Kreslavsky T; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA., Brown FD; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA., Moffett H; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA., Lemieux ME; Bioinfo, Plantagenet, Canada., Kaygusuz Y; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA., Meissner T; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA., Holderried TA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA., Chan S; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch, France. Faculté de Médecine, Université de Strasbourg, Strasbourg, France., Kastner P; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch, France. Faculté de Médecine, Université de Strasbourg, Strasbourg, France., Haining WN; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA., Cantor H; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston MA. harvey_cantor@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2015 Oct 16; Vol. 350 (6258), pp. 334-9.
DOI: 10.1126/science.aad0616
Abstrakt: The maintenance of immune homeostasis requires regulatory T cells (T(regs)). Given their intrinsic self-reactivity, T(regs) must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3(+) CD4 and Qa-1-restricted CD8 T(regs) results in defective regulatory activity and autoimmunity in mice. Helios-deficient T(regs) develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 T(regs) also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. The definition of Helios as a key transcription factor that stabilizes T(regs) in the face of inflammatory responses provides a genetic explanation for a core property of T(regs).
(Copyright © 2015, American Association for the Advancement of Science.)
Databáze: MEDLINE
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