title: IL-21-stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation.
abstract: Plasmacytoid dendritic cells (pDCs) play a crucial role during innate immunity by secreting bulk amounts of type I interferons (IFNs) in response to Toll-like receptor (TLR)-mediated pathogen recognition. In addition, pDCs can also contribute to adaptive immunity by activation of antigen-specific T cells. Furthermore, it is well established that pDCs contribute to the pathogenesis of autoimmune diseases, including lupus. Interleukin-21 (IL-21) is a cytokine produced by activated CD4(+) T and natural killer T (NKT) cells and has a pleiotropic role in immunity by controlling myeloid DC-, NKT-, T-, and B-cell functions. It has remained elusive whether IL-21 affects pDCs. Here we investigate the role of IL-21 in human pDC activation and function and observe that IL-21 activates signal transducer and activator of transcription 3 in line with the finding that pDCs express the IL-21 receptor. Although IL-21 did not affect TLR-induced type I IFNs, IL-6, and TNF-α nor expression of major-histocompatibility-complex class II or costimulatory molecules, IL-21 markedly increased expression of the serine protease granzyme B (GrB). We demonstrate that GrB induction was, in part, responsible for IL-21-mediated downmodulation of CD4(+) T-cell proliferation induced by TLR preactivated pDCs. Collectively, our data provide evidence that pDCs are important cells to consider when investigating the role of IL-21 in immunity or pathogenesis.
authors: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Julien J
authors: JJ
authors: Karrich
authors: Loes C M
authors: LC
authors: Jachimowski
authors: Maho
authors: M
authors: Nagasawa
authors: Angela
authors: A
authors: Kamp
authors: Melania
authors: M
authors: Balzarolo
authors: Monika C
authors: MC
authors: Wolkers
authors: Christel H
authors: CH
authors: Uittenbogaart
authors: S
authors: S
authors: Marieke van Ham
authors: Bianca
authors: B
authors: Blom
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053804:Granzymes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D015854:Up-Regulation; D000098546:Interleukin-21
chemical_list: D016207:Cytokines; D007378:Interleukins; D051193:Toll-Like Receptors; D053804:Granzymes; D000098546:Interleukin-21