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IL-21–stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation

Overview of attention for article published in Blood, February 2013
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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.

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Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

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%