Attridge, K; Kenefeck, R; Wardzinski, L; Qureshi, OS; Wang, CJ; Manzotti, C; Okkenhaug, K; Attridge, K; Kenefeck, R; Wardzinski, L; Qureshi, OS; Wang, CJ; Manzotti, C; Okkenhaug, K; Walker, LS; - view fewer (2014) IL-21 Promotes CD4 T Cell Responses by Phosphatidylinositol 3-Kinase-Dependent Upregulation of CD86 on B Cells. J Immunol , 192 pp. 2195-2201. 10.4049/jimmunol.1302082.

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Abstract

The cytokine IL-21 is a potent immune modulator with diverse mechanisms of action on multiple cell types. IL-21 is in clinical use to promote tumor rejection and is an emerging target for neutralization in the setting of autoimmunity. Despite its clinical potential, the biological actions of IL-21 are not yet fully understood and the full range of effects of this pleiotropic cytokine are still being uncovered. In this study, we identify a novel role for IL-21 as an inducer of the costimulatory ligand CD86 on B lymphocytes. CD86 provides critical signals through T cell-expressed CD28 that promote T cell activation in response to Ag engagement. Expression levels of CD86 are tightly regulated in vivo, being actively decreased by regulatory T cells and increased in response to pathogen-derived signals. In this study, we demonstrate that IL-21 can trigger potent and sustained CD86 upregulation through a STAT3 and PI3K-dependent mechanism. We show that elevated CD86 expression has functional consequences for the magnitude of CD4 T cell responses both in vitro and in vivo. These data pinpoint CD86 upregulation as an additional mechanism by which IL-21 can elicit immunomodulatory effects.

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