title: Epstein-Barr virus-induced gene 3 negatively regulates IL-17, IL-22 and RORgamma t.
abstract: 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.
authors.affiliation: Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT 06877, USA. jianfei.yang@boehringer-ingelheim.com
authors.forename: Jianfei
authors.initials: J
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Tin Min
authors.initials: TM
authors.lastname: Htut
authors.forename: Xinshou
authors.initials: X
authors.lastname: Ouyang
authors.forename: Adedayo
authors.initials: A
authors.lastname: Hanidu
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Sellati
authors.forename: Huiping
authors.initials: H
authors.lastname: Jiang
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Hongxing
authors.initials: H
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Ting
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: Jay C
authors.initials: JC
authors.lastname: Unkeless
authors.forename: Mark E
authors.initials: ME
authors.lastname: Labadia
authors.forename: Martin
authors.initials: M
authors.lastname: Hodge
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010047:Ovalbumin; D011948:Receptors, Antigen, T-Cell; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C097732:EBI3 protein, human; C498833:Foxp3 protein, mouse; C539900:RORC protein, human; C539901:Rorc protein, mouse