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Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 Jan 01; Vol. 190 (1), pp. 58-65. Date of Electronic Publication: 2012 Nov 30. - Publication Year :
- 2013
-
Abstract
- Early growth response gene (Egr)-2 is important for the maintenance of T cell homeostasis and controls the development of autoimmune disease. However, the underlying mechanisms are unknown. We have now discovered that Egr-2, which is induced by TGF-β and IL-6, negatively regulates the expression of IL-17, but not IL-2 or IFN-γ, in effector T cells. In the absence of Egr-2, CD4 T cells produce high levels of Th17 cytokines, which renders mice susceptible to experimental autoimmune encephalomyelitis induction. T cells lacking Egr-2 show increased propensity for Th17, but not Th1 or Th2, differentiation. Control of IL-17 expression and Th17 differentiation by Egr-2 is due to inhibition of Batf, a transcription factor that regulates IL-17 expression and Th17 differentiation. Egr-2 interacts with Batf in CD4 T cells and suppresses its interaction with DNA sequences derived from the IL-17 promoter, whereas the activation of STAT3 and expression of retinoic acid-related orphan receptor γt are unchanged in Th17 cells in the absence of Egr-2. Thus, Egr-2 plays an important role to intrinsically control Th17 differentiation. We also found that CD4 T cells from multiple sclerosis patients have reduced expression of Egr-2 and increased expression of IL-17 following stimulation with anti-CD3 in vitro. Collectively, our results demonstrate that Egr-2 is an intrinsic regulator that controls Th17 differentiation by inhibiting Batf activation, which may be important for the control of multiple sclerosis development.
- Subjects :
- Animals
Basic-Leucine Zipper Transcription Factors antagonists & inhibitors
Basic-Leucine Zipper Transcription Factors physiology
Early Growth Response Protein 2 biosynthesis
Early Growth Response Protein 2 deficiency
HEK293 Cells
Humans
Inflammation immunology
Inflammation metabolism
Inflammation prevention & control
Interleukin-17 genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Th17 Cells cytology
Th17 Cells metabolism
Basic-Leucine Zipper Transcription Factors biosynthesis
Cell Differentiation immunology
Down-Regulation immunology
Early Growth Response Protein 2 physiology
Feedback, Physiological physiology
Interleukin-17 biosynthesis
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 190
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 23203924
- Full Text :
- https://doi.org/10.4049/jimmunol.1200868