Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORgamma t
| Autor: | Jie Zhao, Tin Min Htut, Xinshou Ouyang, Hongxing Li, Adedayo Hanidu, Rosemarie Sellati, Jay C. Unkeless, Jun Li, Shu Zhang, Jianfei Yang, Huabao Xiong, Xiang Li, Adrian T. Ting, Mark E. Labadia, Martin Hodge, Huiping Jiang, Min Yang, Lloyd Mayer |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Ovalbumin Receptors Retinoic Acid Cellular differentiation T-Lymphocytes Immunology Receptors Antigen T-Cell Gene Expression Mice Transgenic Biology T-Lymphocytes Regulatory Article Interleukin 22 Minor Histocompatibility Antigens Interferon-gamma Mice Antigen medicine Immunology and Allergy Animals Interferon gamma Listeriosis Mice Knockout Receptors Thyroid Hormone Tumor Necrosis Factor-alpha Interleukins Interleukin-17 EBI3 Cell Differentiation Forkhead Transcription Factors Nuclear Receptor Subfamily 1 Group F Member 3 Acquired immune system Molecular biology Listeria monocytogenes Mice Inbred C57BL Gene Expression Regulation Tumor necrosis factor alpha Interleukin 17 Spleen medicine.drug |
| Zdroj: | European journal of immunology. 38(5) |
| ISSN: | 0014-2980 |
| Popis: | Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 to form IL-27 and with IL-12p35 to form IL-35. IL-27Ralpha(-/-) 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 RORgamma t 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 RORgamma t as well as protective immunity against L. monocytogenes. |
| Databáze: | OpenAIRE |
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