title: CD4(+)B220(+)TCRγδ(+) T cells produce IL-17 in lupus-prone MRL/lpr mice.
abstract: Systemic lupus erythematosus is an autoimmune disease with comprehensive immune cell disorders. Recent studies suggested that pro-inflammatory cytokine IL-17 plays important role in lupus, leaving the cellular sources and their pathogenic and physiologic characters largely unknown. In the current study, by using lupus-prone MRL/lpr mice, we demonstrated that Th17 response prevails in lupus disease regarding significantly accumulated serum IL-17, increased IL-17-producing splenocytes, and elevated phospho-STAT3 in CD4(+) T cells. Intracellular staining revealed that unusual CD4(+)B220(+) T cells are major IL-17-producing cells, whereas conventional CD4(+)B220(-) T cells are major IFN-γ-producing cells. Subsequent studies showed that CD4(+)B220(+) cells contains both αβ and γδ T cells in the spleen and thymus of MRL/lpr mice. Further study showed that around 60% of γδ T cells in MRL/lpr mice co-express both B220 and CD4 on their surface, and are the major RORγt(+) cells in MRL/lpr mice. Finally, CD4(+)B220(+) T cells alone do not proliferate, but could enhance the proliferation and IFN-γ-production of conventional CD4(+)B220(-) T cells. Our findings suggest the pathogenic role of unusual CD4(+)B220(+) T cells in lupus disease in MRL/lpr mice according to their IL-17-producing ability and stimulatory function for conventional CD4(+)B220(-) T cells.
authors.affiliation: Department of Neurology, Navy Clinical College, Second Military Medical University, Shanghai 200433, China; Department of Neurology, Chinese Navy General Hospital, Beijing 100048, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Department of Geriatric Gastroenterology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Gastroenterology, Chinese People's Liberation Army General Hospital, Beijing 100853, China. Electronic address: wanjun301@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Neurology, Navy Clinical College, Second Military Medical University, Shanghai 200433, China; Department of Neurology, Chinese Navy General Hospital, Beijing 100048, China. Electronic address: qixiaokunnavy@126.com.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Qi
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens
keywords: IL-17; Systemic lupus erythematosus; γδT cells