Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORγt

Jianfei Yang, Min Yang, Tin Min Htut, Xinshou Ouyang, Adedayo Hanidu, Xiang Li, Rosemarie Sellati, Huiping Jiang, Shu Zhang, Hongxing Li, Jie Zhao, Adrian T. Ting, Lloyd Mayer, Jay C. Unkeless, Mark E. Labadia, Martin Hodge, Jun Li, Huabao Xiong

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 to form IL-27 and with IL-12p35 to form IL-35. IL-27Rα-/- mice studies indicate that IL-27 negatively regulates Th17 cell differentiation. However, no EBI3, p28 or p35-deficiency studies that directly address the role of EBI3, p28 or p35 on Th17 cells have been done. Here, we demonstrate that spleen cells derived from EBI3-/- mice produce significantly higher levels of IL-17 as well as IL-22 upon stimulation with OVA. In vitro derived EBI3-/- Th17 cells also produced significantly higher levels of IL-17 and IL-22 than WT cells. The frequency of IL-17-producing cells was also elevated when EBI3-/- cells were cultured under Th17 conditions. In addition, spleen cells from EBI3-/- mice immunized with Listeria monocytogenes produced significantly elevated levels of IL-17 and IL-22. Furthermore, the Th17 transcription factor RORγt was significantly enhanced in EBI3-/- cells. Finally, EBI3-/- mice exhibited a reduced bacterial load following an acute challenge with L. monocytogenes or a re-challenge of previously immunized mice, suggesting that EBI3 negatively regulates both innate and adaptive immunity. Taken together, these data provide direct evidence that EBI3 negatively regulates the expression of IL-17, IL-22 and RORγt as well as protective immunity against L. monocytogenes.

Original languageEnglish (US)
Pages (from-to)1204-1214
Number of pages11
JournalEuropean Journal of Immunology
Volume38
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Cytokines
  • Gene regulation
  • T helper cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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