Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells
Open accessAbstract
The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune responses. Histone deacetylases (HDACs) have been widely described as negative regulators of transcriptional regulation, and in this context, the primarily nuclear protein HDAC11 was shown to repress il-10 gene transcriptional activity in antigen-presenting cells (APCs). Here we report that another HDAC, HDAC6, primarily a cytoplasmic protein, associates with HDAC11 and modulates the expression of IL-10 as a transcriptional activator. To our knowledge, this is the first demonstration of two different HDACs being recruited to the same gene promoter to dictate divergent transcriptional responses. This dynamic interaction results in dynamic changes in the expression of IL-10 and might help to explain the intrinsic plasticity of the APC to determine T-cell activation versus T-cell tolerance.
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HDAC11 associates with HDAC6.
“It has been shown to associate with HDAC6 (Gao et al., 2002; Cheng et al., 2014)”
From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Cheng et al., 2014
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- Authors
- Cheng, F., Lienlaf, M., Perez-Villarroel, P., Wang, H.-W., Lee, C., Woan, K., Woods, D., Knox, T., Bergman, J., Pinilla-Ibarz, J., Kozikowski, A., Seto, E., Sotomayor, E. M., & Villagra, A.
- Affiliations
- Moffitt Cancer Center (US)
- Johns Hopkins University (US)
- University of Illinois Chicago (US)
- Corresponding author
- Sotomayor, Eduardo M.
- Villagra, Alejandro
- ORCID
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 60
- Issue
- 1
- Pages
- 44-53
- ISSN
- 0161-5890 (ISSN-L)
- PMC
- PMC4020151
- OpenAlex
- W1979610433
- Cited by
- 140
- References
- 31
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 9 · 2023: 17 · 2022: 14 · 2021: 12 · 2020: 17 · 2019: 12 · 2018: 16 · 2017: 12 · 2016: 12 · 2015: 4 · 2014: 3
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R21CA184612, R01CA087583, CA134807, R01CA134807, CA153246, R21CA153246, R01CA100850, P50CA168536, CA87583, CA100850, P30CA076292)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- HDAC6, IL-10, antigen-presenting cells, transcriptional regulation, T cell tolerance, T cell activation, anti-inflammatory cytokines
- MeSH terms
- Histone Deacetylase 6, Animals, Antigen-Presenting Cells, Cell Line, Gene Expression Regulation, Histone Deacetylases, Immune Tolerance, Lymphocyte Activation, Macrophages, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Promoter Regions, Genetic, T-Lymphocytes, Transcription, Genetic, Transcriptional Activation, Interleukin-10, Mice, Knockout, RNA Interference, RNA, Small Interfering, Mice
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