ERK differentially regulates Th17- and Treg-cell development and contributes to the pathogenesis of colitis

Houpu Liu, Suxia Yao, Sara Dann-Grice, Hongwei Qin, Charles O. Elson, Yingzi Cong

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Although the development of T-cell subsets is mainly regulated by a master transcriptional regulator and phosphorylation of the STAT protein in response to distinct cytokine stimulation, accumulating data indicate that other signaling pathways are also involved in regulating or fine-tuning T-cell lineage commitment. In this report, we investigated the role of ERK, mitogen-activated protein kinase (MAPK), in Th17 and Treg cell development. We demonstrate that blockade of ERK activation inhibited Th17-cell development while upregulating Treg cells under Th17 polarization conditions. Inhibition of ERK decreased IL-6 induction of RAR-related orphan receptor γt but enhanced TGF-β induction of Foxp3, and ERK inhibitor-treated T cells under Th17 conditions possessed suppressive function in vitro because they produced more IL-10 and TGF-β and inhibited naïve T-cell proliferation and IFN-γ production at levels comparable with that of Treg cells. Furthermore, ERK inhibitor-treated T cells under Th17 polarization conditions had a decreased potency to induce colitis in vivo. Collectively, our data demonstrated that the ERK pathway differentially regulates Th17- and Treg-cell differentiation, and thus interfering with the ERK pathway could represent a therapeutic treatment for inflammatory bowel diseases and other Th17-related autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)1716-1726
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number7
DOIs
StatePublished - Jul 2013

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Th17 Cells
Regulatory T-Lymphocytes
Colitis
T-Lymphocytes
MAP Kinase Signaling System
T-Lymphocyte Subsets
Cell Lineage
Mitogen-Activated Protein Kinases
Inflammatory Bowel Diseases
Interleukin-10
Autoimmune Diseases
Cell Differentiation
Interleukin-6
Phosphorylation
Cell Proliferation
Cytokines
Proteins
Therapeutics

Keywords

  • Colitis
  • ERK
  • Th17
  • Treg

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

ERK differentially regulates Th17- and Treg-cell development and contributes to the pathogenesis of colitis. / Liu, Houpu; Yao, Suxia; Dann-Grice, Sara; Qin, Hongwei; Elson, Charles O.; Cong, Yingzi.

In: European Journal of Immunology, Vol. 43, No. 7, 07.2013, p. 1716-1726.

Research output: Contribution to journalArticle

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AU - Elson, Charles O.

AU - Cong, Yingzi

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