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J Immunol. 2009 Mar 1;182(5):2859-67. doi: 10.4049/jimmunol.0802978.

IL-21 mediates suppressive effects via its induction of IL-10.

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Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.


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.

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