IL-21-stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation
| Autor: | Bianca Blom, Angela M. Kamp, Julien J. Karrich, Maho Nagasawa, Loes C. M. Jachimowski, S. Marieke van Ham, Melania Balzarolo, Christel H. Uittenbogaart, Monika C. Wolkers |
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| Přispěvatelé: | Other departments, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Landsteiner Laboratory, Cell Biology and Histology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell Survival medicine.medical_treatment T cell Immunology macromolecular substances Biology Biochemistry Granzymes Interleukin 21 medicine Humans Cells Cultured Immunobiology Cell Proliferation Innate immune system Interleukins Toll-Like Receptors hemic and immune systems Dendritic Cells Cell Biology Hematology Acquired immune system Up-Regulation Cell biology Granzyme B Cytokine medicine.anatomical_structure Granzyme Child Preschool STAT protein biology.protein Cytokines |
| Zdroj: | Blood, 121(16), 3103-3111. American Society of Hematology |
| ISSN: | 0006-4971 |
| Popis: | 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-alpha nor expression ofmajor-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 |
| Databáze: | OpenAIRE |
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