title: Interleukin-9 Is Associated with Elevated Anti-Double-Stranded DNA Antibodies in Lupus-Prone Mice.
abstract: Interleukin (IL)-9, which is produced mainly by CD4(+) T cells, is implicated in mast cell-related allergic diseases, although its involvement in systemic lupus erythematosus (SLE) pathogenesis remains unclear. Thus, we investigated the presence of IL-9 in lupus-prone MRL/Mp-lpr/lpr (MRL/lpr) mice and examined the role of IL-9 in lupus pathogenesis. Increased levels of IL-9(+) lymphocytes were detected in the spleens and kidneys of MRL/lpr mice and increased IL-9 levels in the spleen correlated with PNA(+) germinal center (GC) cell expansion. The percentage of CD4(+)IL-9(+) (Th9) cells was increased in MRL/lpr mice and serum IL-9 levels were elevated and closely related to the production of antibodies against double-stranded DNA (dsDNA). IL-9 appears to promote B-cell proliferation and immunoglobulin production, which could be blocked by inhibition of signal transducer and activator of transcription 3 (STAT3). Treatment with neutralizing anti-IL-9 antibody in vivo decreased serum anti-dsDNA-antibody titers and alleviated lupus nephritis in MRL/lpr mice. Our findings indicate expansion of Th9 cells in lupus-prone MRL/lpr mice and the correlation of IL-9 with B-cell proliferation and autoantibody production. These findings suggest that IL-9 is a potential therapeutic target for SLE.
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.|Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D016906:Interleukin-9 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism*; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D057134:Antibodies, Neutralizing; D016207:Cytokines; D020381:Interleukin-17; D016906:Interleukin-9; D050796:STAT3 Transcription Factor