Title |
IL-21–stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation
|
---|---|
Published in |
Blood, February 2013
|
DOI | 10.1182/blood-2012-08-452995 |
Pubmed ID | |
Authors |
Julien J. Karrich, Loes C.M. Jachimowski, Maho Nagasawa, Angela Kamp, Melania Balzarolo, Monika C. Wolkers, Christel H. Uittenbogaart, S. Marieke van Ham, Bianca Blom |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 1 | 2% |
Mexico | 1 | 2% |
Unknown | 57 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 15 | 25% |
Student > Ph. D. Student | 13 | 22% |
Student > Master | 5 | 8% |
Professor | 4 | 7% |
Student > Bachelor | 3 | 5% |
Other | 11 | 19% |
Unknown | 8 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 19 | 32% |
Agricultural and Biological Sciences | 12 | 20% |
Immunology and Microbiology | 9 | 15% |
Biochemistry, Genetics and Molecular Biology | 3 | 5% |
Nursing and Health Professions | 2 | 3% |
Other | 5 | 8% |
Unknown | 9 | 15% |