title: IL-21 mediates suppressive effects via its induction of IL-10.
abstract: IL-21 is a pleiotropic cytokine that is required for normal Ig production. We previously showed that IL-21 was elevated in BXSB-Yaa mice with systemic lupus erythematosus. These mice also had elevated IL-10 levels, and we now show that IL-21 induces IL-10 mRNA and protein, suggesting unexpected immunosuppressive activities for IL-21. Indeed, Th1 priming with IL-21 leads to accumulation of cells with immunosuppressive activity, and IL-21 overexpression decreases specific Ab production after immunization in an IL-10-dependent fashion. Moreover, we show that IL-21 signaling is required for maximal induction of IL-10 by IL-6 or IL-27. Overall, our data indicate that IL-21 regulates immune responses at least in part by inducing IL-10 and reveal unanticipated immunosuppressive actions for this cytokine.
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.forename: Hyoung-Pyo
authors.initials: HP
authors.lastname: Kim
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D016753:Interleukin-10; D000098546:Interleukin-21