Abstract

CD4(+) interleukin 17 (IL-17)-producing helper T cells (T(H)17 cells) are instrumental in the immune response to pathogens. However, an overactive T(H)17 response results in tissue inflammation and autoimmunity, and therefore it is important to identify the molecular mechanisms that control the development of T(H)17 cells. IL-2 suppresses such development, but how IL-2 production is actively suppressed during T(H)7 differentiation is not understood. Here we report that under T(H)17-polarizing conditions, the transcription factors STAT3 and AhR upregulated the expression of Aiolos, a member of the Ikaros family of transcription factors. Using Aiolos-deficient mice, we demonstrated that Aiolos silenced the Il2 locus, promoting T(H)17 differentiation in vitro and in vivo. Thus, we have identified a module in the transcriptional program of T(H)17 cells that actively limits IL-2 production and promotes their differentiation.

Links

Publisher Full Text

Authors

Quintana FJ, Jin H, Burns EJ, Nadeau M, Yeste A, Kumar D, Rangachari M, Zhu C, Xiao S, Seavitt J, Georgopoulos K, Kuchroo VK

Institution

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. fquintana@rics.bwh.harvard.edu

Source

Nature immunology 13:8 2012 pg 770-7

MeSH

Animals
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation
Cells, Cultured
Colitis
Gene Expression Regulation
Interferon-gamma
Interleukin-2
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Aryl Hydrocarbon
STAT3 Transcription Factor
Th17 Cells
Trans-Activators

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22751139