Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2008 Jul 1

PMID 18585065

Citations 613

Authors

Xuexian O Yang

Roza Nurieva

Gustavo J Martinez

Hong Soon Kang

Yeonseok Chung

Bhanu P Pappu

Bhavin Shah

Seon Hee Chang

Kimberly S Schluns

Stephanie S Watowich

Xin-Hua Feng

Anton M Jetten

Chen Dong

Affiliations

Soon will be listed here.

Abstract

Regulatory T (Treg) and T helper 17 (Th17) cells were recently proposed to be reciprocally regulated during differentiation. To understand the underlying mechanisms, we utilized a Th17 reporter mouse with a red fluorescent protein (RFP) sequence inserted into the interleukin-17F (IL-17F) gene. Using IL-17F-RFP together with a Foxp3 reporter, we found that the development of Th17 and Foxp3(+) Treg cells was associated in immune responses. Although TGF-beta receptor I signaling was required for both Foxp3 and IL-17 induction, SMAD4 was only involved in Foxp3 upregulation. Foxp3 inhibited Th17 differentiation by antagonizing the function of the transcription factors RORgammat and ROR*. In contrast, IL-6 overcame this suppressive effect of Foxp3 and, together with IL-1, induced genetic reprogramming in Foxp3(+) Treg cells. STAT3 regulated Foxp3 downregulation, whereas STAT3, RORgamma, and ROR* were required for IL-17 expression in Treg cells. Our data demonstrate molecular antagonism and plasticity of Treg and Th17 cell programs.

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