Journal article
Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion
Blood, Vol.115(6), pp.1156-1165
Immunobiology
02/11/2010
DOI: 10.1182/blood-2009-07-235382
PMCID: PMC2920226
PMID: 19965634
Abstract
Human plasmacytoid dendritic cells (pDCs) are crucially involved in the modulation of adaptive T-cell responses in the course of neoplastic, viral, and autoimmune disorders. In several of these diseases elevated extracellular levels of the serine protease granzyme B (GrB) are observed. Here we demonstrate that human pDCs can be an abundant source of GrB and that such GrB
+
pDCs potently suppress T-cell proliferation in a GrB-dependent, perforin-independent manner, a process reminiscent of regulatory T cells. Moreover, we show that GrB expression is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5 and that interleukin-3 (IL-3), a cytokine secreted by activated T cells, plays a central role for GrB induction. Moreover, we find that the immunosuppressive cytokine IL-10 enhances, while Toll-like receptor agonists and CD40 ligand strongly inhibit, GrB secretion by pDCs. GrB-secreting pDCs may play a regulatory role for immune evasion of tumors, antiviral immune responses, and autoimmune processes. Our results provide novel information about the complex network of pDC–T-cell interactions and may contribute to an improvement of prophylactic and therapeutic vaccinations.
Details
- Title: Subtitle
- Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion
- Creators
- Bernd Jahrsdörfer - Institute of Pharmacology of Natural Products and Clinical Pharmacology andAngelika Vollmer - Department of Pediatrics, University of Ulm, Ulm, GermanySue E Blackwell - Department of Internal Medicine and Holden Comprehensive Cancer Center, University of Iowa, Iowa CityJulia Maier - Department of Pediatrics, University of Ulm, Ulm, GermanyKai Sontheimer - Institute of Pharmacology of Natural Products and Clinical Pharmacology andThamara Beyer - Institute of Pharmacology of Natural Products and Clinical Pharmacology andBirgit Mandel - Department of Pediatrics, University of Ulm, Ulm, GermanyOleg Lunov - Institute of Pharmacology of Natural Products and Clinical Pharmacology andKyrylo Tron - Institute of Biophysics, University of Ulm, Ulm, Germany; andG. Ulrich Nienhaus - Institute of Biophysics, University of Ulm, Ulm, Germany; andThomas Simmet - Institute of Pharmacology of Natural Products and Clinical Pharmacology andKlaus-Michael Debatin - Department of Pediatrics, University of Ulm, Ulm, GermanyGeorge J Weiner - Department of Internal Medicine and Holden Comprehensive Cancer Center, University of Iowa, Iowa CityDorit Fabricius - Department of Pediatrics, University of Ulm, Ulm, Germany
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.115(6), pp.1156-1165
- Publisher
- American Society of Hematology
- Series
- Immunobiology
- DOI
- 10.1182/blood-2009-07-235382
- PMID
- 19965634
- PMCID
- PMC2920226
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 02/11/2010
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984094395402771
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