Publication Date:
2015-10-17
Description:
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).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627635/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627635/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Hye-Jung -- Barnitz, R Anthony -- Kreslavsky, Taras -- Brown, Flavian D -- Moffett, Howell -- Lemieux, Madeleine E -- Kaygusuz, Yasemin -- Meissner, Torsten -- Holderried, Tobias A W -- Chan, Susan -- Kastner, Philippe -- Haining, W Nicholas -- Cantor, Harvey -- R01 AI037562/AI/NIAID NIH HHS/ -- R01AI37562/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):334-9. doi: 10.1126/science.aad0616.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; 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. ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. ; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. ; Bioinfo, Plantagenet, Canada. ; Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Universite de Strasbourg, 67404 Illkirch, France. Faculte de Medecine, Universite de Strasbourg, Strasbourg, France. ; 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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472910" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Autoimmunity/genetics/*immunology
;
CD8-Positive T-Lymphocytes/*immunology
;
DNA-Binding Proteins/*biosynthesis/genetics
;
Forkhead Transcription Factors/immunology
;
Gene Expression
;
Kidney/immunology
;
Liver/immunology
;
Lymphocyte Activation
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Pancreas/immunology
;
STAT5 Transcription Factor/metabolism
;
T-Lymphocytes, Regulatory/*immunology
;
Transcription Factors/*biosynthesis/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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