The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection
Open accessAbstract
Regulated by histone acetyltransferases and deacetylases (HDACs), histone acetylation is a key epigenetic mechanism controlling chromatin structure, DNA accessibility, and gene expression. HDAC inhibitors induce growth arrest, differentiation, and apoptosis of tumor cells and are used as anticancer agents. Here we describe the effects of HDAC inhibitors on microbial sensing by macrophages and dendritic cells in vitro and host defenses against infection in vivo. HDAC inhibitors down-regulated the expression of numerous host defense genes, including pattern recognition receptors, kinases, transcription regulators, cytokines, chemokines, growth factors, and costimulatory molecules as assessed by genome-wide microarray analyses or innate immune responses of macrophages and dendritic cells stimulated with Toll-like receptor agonists. HDAC inhibitors induced the expression of Mi-2β and enhanced the DNA-binding activity of the Mi-2/NuRD complex that acts as a transcriptional repressor of macrophage cytokine production. In vivo, HDAC inhibitors increased the susceptibility to bacterial and fungal infections but conferred protection against toxic and septic shock. Thus, these data identify an essential role for HDAC inhibitors in the regulation of the expression of innate immune genes and host defenses against microbial pathogens.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“As drug inhibition of cellular deacetylases strongly attenuates pathogen-and immunogen-induced immune responses (139–141), it is tempting to speculate that acetylation plays a key role in modulating immune signaling pathways.”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [140]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Delaloye, J., Roger, T., Steiner, Q., Roy, D. L., Reymond, M. K., Akira, S., Pétrilli, V., Gómez, C. E., Perdiguero, B., Tschopp, J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000480 · Cited by 307
Self-citationRetractedKorn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Interleukin-12 and the regulation of innate resistance and adaptive immunity
Trinchieri, G. (2003) · Nature reviews. Immunology · doi:10.1038/nri1001 · Cited by 4,007
Anticancer activities of histone deacetylase inhibitors
Bolden, J. E., Peart, M. J., & Johnstone, R. W. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2133 · Cited by 2,919
Recognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862
Haberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,600
Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
Minucci, S., & Pelicci, P. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1779 · Cited by 2,234
Macrophage migration inhibitory factor: a regulator of innate immunity
Calandra, T., & Roger, T. (2003) · Nature reviews. Immunology · doi:10.1038/nri1200 · Cited by 1,782
Self-citationHistone deacetylase inhibitors: molecular mechanisms of action
Xu, W. S., Parmigiani, R. B., & Marks, P. A. (2007) · Oncogene · doi:10.1038/sj.onc.1210620 · Cited by 1,542
Extracellular histones are major mediators of death in sepsis
Xu, J., Zhang, X., Pelayo, R., Monestier, M., Ammollo, C. T., Semeraro, F., Taylor, F. B., Esmon, N. L., Lupu, F., & Esmon, C. T. (2009) · Nature Medicine · doi:10.1038/nm.2053 · Cited by 1,540
The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men
Yang, X., & Seto, E. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2346 · Cited by 1,277
Harmful molecular mechanisms in sepsis
Rittirsch, D., Flierl, M. A., & Ward, P. A. (2008) · Nature reviews. Immunology · doi:10.1038/nri2402 · Cited by 1,230
TYPE I INTERFERONS (α/β) IN IMMUNITY AND AUTOIMMUNITY
Theofilopoulos, A. N., Baccalà, R., Beutler, B., & Kono, D. H. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115843 · Cited by 1,205
Marks, P. A., & Breslow, R. (2007) · Nature Biotechnology · doi:10.1038/nbt1272 · Cited by 1,198
Interferons at age 50: past, current and future impact on biomedicine
Borden, E. C., Sen, G. C., Uze, G., Silverman, R. H., Ransohoff, R. M., Foster, G. R., & Stark, G. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2422 · Cited by 1,154
Histone deacetylases and cancer
Glozak, M. A., & Seto, E. (2007) · Oncogene · doi:10.1038/sj.onc.1210610 · Cited by 1,031
Kelly, W. K., O’Connor, O. A., Krug, L. M., Chiao, J. H., Heaney, M. L., Curley, T., MacGregor‐Cortelli, B., Tong, W. P., Secrist, J. P., Schwartz, L. B., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.14.167 · Cited by 906
Human CD25highFoxp3pos regulatory T cells differentiate into IL-17–producing cells
Koenen, H. J. P. M., Smeets, R. L., Vink, P. M., van Rijssen, E., Boots, A. M. H., & Joosten, I. (2008) · Blood · doi:10.1182/blood-2008-01-133967 · Cited by 756
Dixon, W. G., Watson, K. D., Lunt, M., Hyrich, K. L., Silman, A. J., & Symmons, D. P. M. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21978 · Cited by 753
MIF regulates innate immune responses through modulation of Toll-like receptor 4
Roger, T., David, J. R., Glauser, M. P., & Calandra, T. (2001) · Nature · doi:10.1038/414920a · Cited by 586
Self-citationHost–pathogen interactions in sepsis
van der Poll, T., & Opal, S. M. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70265-7 · Cited by 568
Host Innate Immune Receptors and Beyond: Making Sense of Microbial Infections
Ishii, K. J., Koyama, S., Nakagawa, A., Coban, C., & Akira, S. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.05.003 · Cited by 509
Ramirez-Carrozzi, V. R., Nazarian, A. A., Li, C. C., Gore, S. L., Sridharan, R., Imbalzano, A. N., & Smale, S. T. (2006) · Genes & Development · doi:10.1101/gad.1383206 · Cited by 422
Ryan, Q. C., Headlee, D. J., Acharya, M. R., Sparreboom, A., Trepel, J. B., Ye, Z., Figg, W. D., Hwang, K., Chung, E. J., Murgo, A. J., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.188 · Cited by 412
Clinical Studies of Histone Deacetylase Inhibitors
Prince, H. M., Bishton, M. J., & Harrison, S. J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2785 · Cited by 358
Nusinzon, I., & Horvath, C. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2433987100 · Cited by 301
Gojo, I., Jiemjit, A., Trepel, J., Sparreboom, A., Figg, W., Rollins, S., Tidwell, M. L., Greer, J., Chung, E., Lee, M.-J., et al. (2007) · Blood · doi:10.1182/blood-2006-05-021873 · Cited by 281
Tumour necrosis factor antagonists: structure, function, and tuberculosis risks
Wallis, R. S. (2008) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(08)70227-5 · Cited by 275
Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4
Roger, T., Froidevaux, C., Roy, D. L., Reymond, M. K., Chanson, A.-L., Mauri, D., Burns, K., Riederer, B. M., Akira, S., & Calandra, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808146106 · Cited by 267
Self-citationReddy, P. R., Sun, Y., Toubai, T., Duran‐Struuck, R., Clouthier, S. G., Weisiger, E., Maeda, Y., Tawara, I., Krijanovski, O. I., Gatza, E., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34712 · Cited by 267
Candelaria, M., Gallardo‐Rincón, D., Arce, C., Cetina, L., Aguilar-Ponce, J. L., Arrieta, O. G., González‐Fierro, A., Chávez-Blanco, A. D., de la Cruz-Hernandez, E., Camargo, M. F. V. C., et al. (2007) · Annals of Oncology · doi:10.1093/annonc/mdm204 · Cited by 256
Aung, H. T., Schroder, K., Himes, S. R., Brion, K., van Zuylen, W. J., Trieu, A., Suzuki, H., Hayashizaki, Y., Hume, D. A., Sweet, M. J., et al. (2006) · The FASEB Journal · doi:10.1096/fj.05-5360com · Cited by 229
Brogdon, J. L., Xu, Y., Szabo, S. J., An, S., Buxton, F., Cohen, D., & Huang, Q. (2006) · Blood · doi:10.1182/blood-2006-04-019711 · Cited by 226
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling
Cao, W., Bao, C., Padalko, E. Y., & Lowenstein, C. J. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071728 · Cited by 188
Roger, T., Chanson, A., Knaup‐Reymond, M., & Calandra, T. (2005) · European Journal of Immunology · doi:10.1002/eji.200535413 · Cited by 184
Self-citationBode, K. A., Schroder, K., Hume, D. A., Ravasi, T., Heeg, K. M., Sweet, M. J., & Dalpke, A. H. (2007) · Immunology · doi:10.1111/j.1365-2567.2007.02678.x · Cited by 180
The role of type I interferons in non‐viral infections
Bogdan, C., Mattner, J., & Schleicher, U. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00207.x · Cited by 178
Thomas, K. E., Galligan, C. L., Newman, R. D., Fish, E. N., & Vogel, S. N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604958200 · Cited by 153
A pervasive role of histone acetyltransferases and deacetylases in an NF-κB-signaling code
Calao, M., Burny, A., Quivy, V., Dekoninck, A., & Lint, C. M. V. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.04.015 · Cited by 144
Nusinzon, I., & Horvath, C. M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.8.3106-3113.2006 · Cited by 139
Galli, M., Salmoiraghi, S., Golay, J., Gozzini, A., Crippa, C., Pescosta, N., & Rambaldi, A. (2009) · Annals of Hematology · doi:10.1007/s00277-009-0793-8 · Cited by 101
Reilly, C. M., Thomas, M. R., Gogal, R. M., Olgun, S., Santo, A., Sodhi, R., Samy, E. T., Peng, S. L., Gilkeson, G. S., & Mishra, N. (2008) · Journal of Autoimmunity · doi:10.1016/j.jaut.2008.04.020 · Cited by 99
Roy, D. L., Padova, F. D., Adachi, Y., Glauser, M. P., Calandra, T., & Heumann, D. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.5.2759 · Cited by 94
Self-citationA BAF-centred view of the immune system
Chi, T. H. (2004) · Nature reviews. Immunology · doi:10.1038/nri1501 · Cited by 84
Rocca, A., Minucci, S., Tosti, G., Croci, D., Contegno, F., Ballarini, M., Nolè, F., Munzone, E., Salmaggi, A., Goldhirsch, A., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604817 · Cited by 79
Cytokines as Therapeutic Targets: Advances and Limitations
Scheinecker, C., Redlich, K., & Smolen, J. S. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.005 · Cited by 78
Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
Bosisio, D., Vulcano, M., Prete, A. D., Sironi, M., Salvi, V., Salogni, L., Riboldi, E., Leoni, F., Dinarello, C. A., Girolomoni, G., et al. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0708401 · Cited by 72
Lu, X., Kovalev, G. I., Chang, H., Kallin, E. M., Knudsen, G., Li, X., Mishra, N., Ruiz, P., Li, E., Su, L., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801275200 · Cited by 63
Lugrin, J., Ding, X. C., Roy, D. L., Chanson, A.-L., Sweep, F. C. G. J., Calandra, T., & Roger, T. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.09.007 · Cited by 51
Self-citationMiconnet, I., & Pantaleo, G. (2008) · Vaccine · doi:10.1016/j.vaccine.2008.05.028 · Cited by 19
Self-citation
Cited by
Sorted by citations
Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322269111 · Cited by 2,175
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
Fuster, J. J., MacLauchlan, S., Zuriaga, M. A., Polackal, M. N., Ostriker, A. C., Chakraborty, R., Wu, C.-L., Sano, S., Muralidharan, S., Rius, C., et al. (2017) · Science · doi:10.1126/science.aag1381 · Cited by 1,536
Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach
Hotchkiss, R. S., Monneret, G., & Payen, D. M. (2013) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(13)70001-x · Cited by 1,483
The role of short-chain fatty acids in immunity, inflammation and metabolism
Yao, Y., Cai, X. T., Fei, W., Ye, Y., Zhao, M., & Zheng, C. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1854675 · Cited by 793
Amino Assets: How Amino Acids Support Immunity
Kelly, B. L., & Pearce, E. L. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.010 · Cited by 666
Metadata
- Authors
- Roger, T., Lugrin, J., Le Roy, D., Goy, G., Mombelli, M., Koessler, T., Ding, X. C., Chanson, A.-L., Reymond, M. K., Miconnet, I., Schrenzel, J., François, P., & Calandra, T.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland;
- University Hospital of Geneva (CH)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-01-27
- Volume
- 117
- Issue
- 4
- Pages
- 1205-1217
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2066887945
- Cited by
- 341
- References
- 51
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 17 · 2022: 23 · 2021: 23 · 2020: 26 · 2019: 18 · 2018: 24 · 2017: 23 · 2016: 38 · 2015: 23 · 2014: 28 · 2013: 28 · 2012: 24
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- histone deacetylase inhibitors, innate immunity, TLR agonists, macrophages, dendritic cells, histone acetylation, epigenetic regulation, NuRD complex, host defense genes, cytokine production, bacterial infection susceptibility, fungal infection susceptibility, septic shock, pattern recognition receptors
- MeSH terms
- Animals, Cells, Cultured, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Gene Expression Regulation, Humans, Immunity, Innate, Infections, Macrophages, Mice, Inbred BALB C, Down-Regulation, Gene Expression Profiling, Microarray Analysis, Toll-Like Receptors, Mice, Histone Deacetylase Inhibitors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
