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Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion
Open accessAbstract
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.
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“Differential gene analyses showed that pDCs were enriched in proinflammatory genes (MZB1, SPIB and UGCG), enabling them to secrete high amounts of IFNα and genes such as TLR7 and GZMB27, reported to mediate inflammation resolution and suppression of T cell expansion, respectively (Fig. 4c,d).”
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Cites
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.-H., Homey, B., Cao, W., Wang, Y.-H., Su, B., Nestle, F. O., et al. (2007) · Nature · doi:10.1038/nature06116 · Cited by 1,910
Plasmacytoid dendritic cells in immunity
Colonna, M., Trinchieri, G., & Liu, Y. (2004) · Nature Immunology · doi:10.1038/ni1141 · Cited by 1,659
IPC: Professional Type 1 Interferon-Producing Cells and Plasmacytoid Dendritic Cell Precursors
Liu, Y.-J. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115633 · Cited by 1,618
Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
Gilliet, M., Cao, W., & Liu, Y.-J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2358 · Cited by 1,190
Grouard, G., Rissoan, M., Filgueira, L., Durand, I., Banchereau, J., & Liu, Y.-J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.6.1101 · Cited by 1,187
Granzyme B and Perforin Are Important for Regulatory T Cell-Mediated Suppression of Tumor Clearance
Cao, X., Cai, S. F., Fehniger, T. A., Song, J., Collins, L. I., Piwnica-Worms, D. R., & Ley, T. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.08.014 · Cited by 1,117
Gondek, D. C., Lu, L., Quezada, S. A., Sakaguchi, S., & Noelle, R. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.4.1783 · Cited by 943
Death by a Thousand Cuts: Granzyme Pathways of Programmed Cell Death
Chowdhury, D., & Lieberman, J. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090404 · Cited by 705
Antigen-presentation properties of plasmacytoid dendritic cells.
Villadangos, J., & Young, L. J. (2008) · Immunity · doi:10.1016/j.immuni.2008.09.002 · Cited by 577
Dendritic cells: Understanding immunogenicity
Steinman, R. M. (2007) · European Journal of Immunology · doi:10.1002/eji.200737400 · Cited by 413
Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes
Stefanová, I., Dorfman, J. R., & Germain, R. N. (2002) · Nature · doi:10.1038/nature01146 · Cited by 389
New Paradigm for Lymphocyte Granule-mediated Cytotoxicity
Froelich, C. J., Orth, K., Turbov, J. M., Seth, P. K., Gottlieb, R. A., BABIOR, B. M., Shah, G. M., Bleackley, R. C., Dixit, V. M., & Hanna, W. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.46.29073 · Cited by 358
Hadeiba, H., Sato, T., Habtezion, A., Oderup, C., Pan, J., & Butcher, E. C. (2008) · Nature Immunology · doi:10.1038/ni.1658 · Cited by 320
Human and Mouse Granzyme A Induce a Proinflammatory Cytokine Response
Metkar, S. S., Menaa, C., Pardo, J., Wang, B., Wallich, R., Freudenberg, M. A., Kim, S. H., Raja, S. M., Shi, L. F., Simon, M. M., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.08.014 · Cited by 304
Recent developments in the transcriptional regulation of cytolytic effector cells
Glimcher, L. H., Townsend, M. J., Sullivan, B. M., & Lord, G. M. (2004) · Nature reviews. Immunology · doi:10.1038/nri1490 · Cited by 293
Granzyme B: a natural born killer
Lord, S. J., Rajotte, R. V., Korbutt, G. S., & Bleackley, R. C. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00044.x · Cited by 289
Rissoan, M., Duhen, T., Bridon, J., Bendriss‐Vermare, N., Péronne, C., Vis, B. D. S., Brière, F., & Bates, E. E. M. (2002) · Blood · doi:10.1182/blood-2002-02-0638 · Cited by 251
Entry and Trafficking of Granzyme B in Target Cells During Granzyme B-Perforin–Mediated Apoptosis
Pinkoski, M. J., Hobman, M., Heibein, J. A., Tomaselli, K. J., Feng, L., Seth, P. K., Froelich, C. J., & Bleackley, R. C. (1998) · Blood · doi:10.1182/blood.v92.3.1044 · Cited by 215
Groß, C. C., Kolch, W., DeMaio, A., Arispe, N. J., & Multhoff, G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302644200 · Cited by 193
Beckebaum, S., Zhang, X., Chen, X., Yu, Z., Frilling, A., Dworacki, G., Grosse‐Wilde, H., Broelsch, C. E., Gerken, G., & Cicinnati, V. R. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0872 · Cited by 181
Human parvovirus B19 infection and autoimmunity
Lunardi, C., Tinazzi, E., Bason, C., Dolcino, M., Corrocher, R., & Puccetti, A. (2008) · Autoimmunity Reviews · doi:10.1016/j.autrev.2008.07.005 · Cited by 168
Tschopp, C. M., Spiegl, N., Didichenko, S. A., Luttmann, W., Julius, P., Virchow, J. C., Jr., Hack, C. E., & Dahinden, C. A. (2006) · Blood · doi:10.1182/blood-2006-03-010348 · Cited by 167
Jahrsdörfer, B., Blackwell, S. E., Wooldridge, J. E., Huang, J., Andreski, M. W., Jacobus, L., Taylor, C. M., & Weiner, G. J. (2006) · Blood · doi:10.1182/blood-2006-03-014001 · Cited by 156
Self-citationVermi, W., Lonardi, S., Morassi, M., Rossini, C., Tardanico, R., Venturini, M., Sala, R., Tincani, A., Poliani, P. L., Calzavara‐Pinton, P., et al. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.06.013 · Cited by 155
Role of Natural Interferon-α Producing Cells (Plasmacytoid Dendritic Cells) in Autoimmunity
Rönnblom, L., Eloranta, M., & Alm, G. V. (2003) · Autoimmunity · doi:10.1080/08916930310001602128 · Cited by 137
IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences
Duramad, O., Fearon, K. L., Chan, J. H., Kanzler, H., Marshall, J. D., Coffman, R. L., & Barrat, F. J. (2003) · Blood · doi:10.1182/blood-2003-07-2465 · Cited by 136
Granzyme B Is Critical for T Cell Receptor-Induced Cell Death of Type 2 Helper T Cells
Devadas, S., Das, J., Liu, C., Zhang, L., Roberts, A. I., Pan, Z., Moore, P. A., Das, G., & Shi, Y. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.011 · Cited by 132
Ge, Q., Rao, V. P., Cho, B. K., Eisen, H. N., & Chen, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1728 · Cited by 132
The role of innate immune responses in autoimmune disease development
Waldner, H. (2009) · Autoimmunity Reviews · doi:10.1016/j.autrev.2008.12.019 · Cited by 127
Hagn, M., Schwesinger, E., Ebel, V., Sontheimer, K., Maier, J., Beyer, T., Syrovets, T., Laumonnier, Y., Fabricius, D., Simmet, T., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901066 · Cited by 126
Self-citationExtracellular granzymes: current perspectives
Buzza, M. S., & Bird, P. I. (2006) · Biological Chemistry · doi:10.1515/bc.2006.106 · Cited by 124
Recruitment of dendritic cells in oral lichen planus
Santoro, A., Majorana, A., Roversi, L., Gentili, F., Marrelli, S., Vermi, W., Bardellini, E., Sapelli, P., & Facchetti, F. (2005) · The Journal of Pathology · doi:10.1002/path.1699 · Cited by 119
Strik, M. C. M., de Koning, P. J. A., Kleijmeer, M. J., Bladergroen, B. A., Wolbink, A. M., Griffith, J. M., Wouters, D., Fukuoka, Y., Schwartz, L. B., Hack, C. E., et al. (2007) · Molecular Immunology · doi:10.1016/j.molimm.2007.03.024 · Cited by 116
Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by chondrocytes.
Froelich, C. J., Zhang, X., Turbov, J. M., Hudig, D., Winkler, U., & Hanna, W. L. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.12.7161 · Cited by 115
Rheumatoid arthritis synovium contains plasmacytoid dendritic cells
Cavanagh, L. L., Boyce, A., Smith, L., Padmanabha, J., Filgueira, L., Pietschmann, P., & Thomas, R. (2005) · Arthritis Research & Therapy · doi:10.1186/ar1467 · Cited by 110
Killing of target cells by redirected granzyme B in the absence of perforin
Kurschus, F. C., Kleinschmidt, M., Fellows, E., Dornmair, K., Rudolph, R., Lilie, H., & Jenne, D. E. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00187-5 · Cited by 87
Loeb, C. R. K., Harris, J. L., & Craik, C. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604544200 · Cited by 82
CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells
Marschner, A., Rothenfußer, S., Hornung, V., Prell, D., Krug, A., Kerkmann, M., Wellisch, D., Poeck, H., Greinacher, A., Giese, T., et al. (2005) · European Journal of Immunology · doi:10.1002/eji.200425721 · Cited by 79
Korthals, M., Safaian, N., Kronenwett, R., Maihöfer, D., Schott, M., Papewalis, C., Blanco, E. D., Winter, M., Czibere, A. G., Haas, R. R., et al. (2007) · Journal of Translational Medicine · doi:10.1186/1479-5876-5-46 · Cited by 78
The role of CD40 in peripheral T cell tolerance and immunity
Diehl, L., den Boer, A. T., van der Voort, E. I. H., Melief, C. J. M., Offringa, R., & Toes, R. E. M. (2000) · Journal of Molecular Medicine · doi:10.1007/s001090000126 · Cited by 76
Non‐apoptotic functions of granzymes
Romero, V., & Andrade, F. (2008) · Tissue Antigens · doi:10.1111/j.1399-0039.2008.01013.x · Cited by 68
On the role of self‐recognition in T cell responses to foreign antigen
Štefanová, I., Dorfman, J. R., Tsukamoto, M., & Germain, R. N. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00006.x · Cited by 66
Ganor, Y., Teichberg, V. I., & Levite, M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.2.683 · Cited by 63
Jähn, P., Zaenker, K. S., Schmitz, J., & Dzionek, A. (2008) · European Journal of Immunology · doi:10.1002/eji.200737552 · Cited by 56
Berthou, C., Marolleau, J., Lafaurie, C., Soulié, A., Cortivo, L. D., Bourge, J. F., Benbunan, M., & Sasportes, M. (1995) · Blood · doi:10.1182/blood.v86.9.3500.bloodjournal8693500 · Cited by 56
Poulopoulou, C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2007 · Cited by 49
Regulation of interleukin 3 gene induction in normal human T cells.
Guba, S. C., Stella, G., Turka, L. A., June, C. H., Thompson, C. B., & Emerson, S. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114352 · Cited by 47
Granzyme B-mediated degradation of T-cell receptor zeta chain.
Wieckowski, E. U., Wang, G.-Q., Gastman, B., Goldstein, L. A., & Rabinowich, H. (2002) · PubMed · Cited by 45
Facchetti, F., Vermi, W., Santoro, A., Vergoni, F., Chilosi, M., & Doglioni, C. (2003) · The American Journal of Surgical Pathology · doi:10.1097/00000478-200311000-00015 · Cited by 38
The role of interleukin-3 in classical Hodgkin's disease
Aldinucci, D., Olivo, K., Lorenzon, D., Poletto, D., Gloghini, A., Carbone, A., & Pinto, A. (2004) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190400013712 · Cited by 37
Mustea, A., Braicu, E. I., Koensgen, D., Yuan, S., Sun, P., Stamatian, F. V., Lichtenegger, W., Chen, F. C.-K., Chekerov, R., & Sehouli, J. (2008) · Cytokine · doi:10.1016/j.cyto.2008.10.019 · Cited by 37
Fabricius, D., O'Dorisio, M. S., Blackwell, S. E., & Jahrsdörfer, B. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.5920 · Cited by 35
Self-citationPhysiological Role of Plasmacytoid Dendritic Cells and Their Potential Use in Cancer Immunity
Schettini, J. L., & Mukherjee, P. (2008) · Clinical and Developmental Immunology · doi:10.1155/2008/106321 · Cited by 32
Autoimmunity in Coxsackievirus Infection
Rose, N. R. (2008) · Springer eBooks · doi:10.1007/978-3-540-75546-3_14 · Cited by 32
Important role of interleukin‐3 in the early phase of collagen‐induced arthritis
Brühl, H., Cihak, J., Niedermeier, M., Denzel, A., Gomez, M. R., Talke, Y., Goebel, N., Plachý, J., Stangassinger, M., & Mack, M. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24441 · Cited by 30
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Metadata
- Authors
- Jahrsdörfer, B., Vollmer, A., Blackwell, S. E., Maier, J., Sontheimer, K., Beyer, T., Mandel, B., Lunov, O., Tron, K., Nienhaus, G. U., Simmet, T., Debatin, K.-M., Weiner, G. J., & Fabricius, D.
- Affiliations
- Universität Ulm (DE)
- University of Iowa (US)
- Institute of Pharmacology (CZ)
- Karlsruhe Institute of Technology (DE)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-02-11
- Volume
- 115
- Issue
- 6
- Pages
- 1156-1165
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2920226
- OpenAlex
- W2018280156
- Cited by
- 180
- References
- 57
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 11 · 2023: 10 · 2022: 18 · 2021: 6 · 2020: 17 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 17 · 2012: 11
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leuka
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Universität Ulm
- National Cancer Institute (P50CA97274, P50CA097274)
- European Social Fund
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- granzyme B, plasmacytoid dendritic cells, T cell suppression, regulatory T cells, JAK1, STAT3, STAT5, interleukin-3, IL-10, TLR agonists, CD40 ligand, transcriptional regulation, tumor immune evasion, antiviral immunity, autoimmune disease, prophylactic and therapeutic vaccination
- MeSH terms
- Arthritis, Juvenile, Cell Differentiation, Cells, Cultured, Child, Cytotoxicity, Immunologic, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Interleukin-3, Lymphocyte Activation, RNA, Messenger, T-Lymphocytes, Blotting, Western, Signal Transduction, Reverse Transcriptase Polymerase Chain Reaction, Cell Proliferation, STAT3 Transcription Factor, STAT5 Transcription Factor, Granzymes
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