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Cited by 460T-cell and B-cell ImmunologyHistone Deacetylase Inhibitors ResearchImmunotherapy and Immune Responses

The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance

Open access
Villagra, Alejandro, Cheng, Fengdong, Wang, Hong-Wei, Suarez, Ildelfonso, Glozak, Michelle, Maurin, Michelle, Nguyen, Danny, Wright, Kenneth L +5 more·2009·Nature Immunology
DOI 10.1038/ni.1673PMC PMC3925685
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Abstract

Antigen-presenting cells (APCs) induce T cell activation as well as T cell tolerance. The molecular basis of the regulation of this critical 'decision' is not well understood. Here we show that HDAC11, a member of the HDAC histone deacetylase family with no prior defined physiological function, negatively regulated expression of the gene encoding interleukin 10 (IL-10) in APCs. Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells. Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses. Thus, HDAC11 represents a molecular target that influences immune activation versus immune tolerance, a critical 'decision' with substantial implications in autoimmunity, transplantation and cancer immunotherapy.

AI snapshot

Written from the paper’s full text.

TL;DR

HDAC11 is identified as a negative transcriptional regulator of IL-10 in antigen-presenting cells, acting mainly at the distal Il10 promoter and requiring its deacetylase activity. Manipulating HDAC11 changes APC inflammatory status and alters priming versus tolerance of antigen-specific CD4+ T cells.

Key findings

  • Overexpression of HDAC11 inhibited LPS-induced IL-10 mRNA in RAW264.7 macrophages, primary mouse macrophages, human dendritic cells and THP-1 cells, while increasing IL-12 mRNA in several of these APC populations; HDAC11 knockdown or stable HDAC11-deficient RAW264.7 clones showed the opposite IL-10 effect.
  • HDAC11 acted at the distal Il10 promoter: HDAC11 was detected mainly in the distal region (positions −807 to −1653), and adding this distal Il10 segment to the short Il12 promoter (−1 to −756) conferred strong HDAC11-mediated inhibition. HDAC11 was not detected on the Il12 promoter.
  • Intact enzymatic activity was required: wild-type HDAC11 inhibited IL-10 mRNA, whereas an HDAC11 mutant lacking the deacetyltransferase domain failed to inhibit and instead increased IL-10 mRNA, suggesting dominant-negative action.
  • Functionally, HDAC11-overexpressing macrophages expressed more CD86 and CD40, produced less IL-10 and more IL-12, activated naive hemagglutinin-specific CD4+ T cells more strongly, and restored IL-2 and IFN-γ production in tolerant CD4+ T cells; APCs lacking HDAC11 impaired antigen-specific CD4+ T cell responses.

Methods

  • Used mouse RAW264.7 macrophages, primary mouse peritoneal macrophages, human THP-1 monocytic cells and human monocyte-derived dendritic cells; BALB/c mice and influenza hemagglutinin TCR-transgenic mice were used for T cell studies.
  • Overexpressed Flag- and GFP-tagged HDAC4–HDAC11 via adenovirus, knocked down HDAC11 with lentiviral shRNA, and used Il10, Il12 and chimeric Il10-Il12 luciferase reporter assays, ChIP, real-time RT-PCR, immunoblot, ELISA and flow cytometry.
  • mRNA was normalized to GAPDH with the Pfaffl method; assays were done in triplicate and repeated at least three times; T cell cytokine production was expressed as pg/ml per 1 × 10² clonotype-positive CD4+ T cells.

Limitations

  • The paper does not state limitations.
  • Evident from the text: most mechanistic work was done in transformed cell lines and in vitro primary APCs, with human data limited largely to mRNA measurements in dendritic cells and THP-1 cells.
  • Evident from the text: HDAC11 was manipulated in APCs in vitro, while the tolerance model involved in vivo peptide-induced T cell tolerance; the proposed distal-to-proximal chromatin “scaffolding” mechanism is presented as plausible rather than directly demonstrated.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/ni.1673

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 13 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Knockdown of HDAC11 in PEMs increases IL-10 mRNA expression in response to LPS relative to nontargeting shRNA.

    “Transduction of PEMs with short hairpin RNA (shRNA) specific for mouse HDAC11 resulted in higher expression of IL-10 mRNA in response to LPS stimulation relative to that of PEMs transduced with nontargeting shRNA (Fig. 2d).”
    Quote in the paperSubstantial claim
  • Findingown data

    Overexpression of HDAC11 increases IL-12 mRNA in THP-1 human monocytic cells.

    “Similarly, we also noted less IL-10 mRNA and more IL-12 mRNA in primary human dendritic cells (Fig. 2b) and THP-1 human monocytic cells (Fig. 2c) overexpressing HDAC11.”
    Quote in the paperSubstantial claim
  • Findingown data

    Overexpression of HDAC11 inhibits Il10 promoter-driven luciferase activity in LPS-stimulated RAW264.7 cells.

    “only HDAC11 overexpression resulted in the inhibition of luciferase activity in response to LPS stimulation (Fig. 1b).”
    • Also stated in: § HDAC 11 interacts with the Il10 promoter · boosted
      “There was again strong inhibition of lucifease activity in LPS-stimulated cells transfected with the Il10 reporter gene and overexpressing HDAC11 (Fig. 3a).”
    Quote in the paperSubstantial claim
  • Findingown data

    Overexpression of HDAC4, HDAC5, HDAC7, HDAC8, HDAC9 or HDAC10 does not affect IL-10 mRNA expression in LPS-stimulated RAW264.7 cells.

    “Infection of macrophages with adenovirus encoding HDAC4, HDAC5, HDAC7, HDAC8, HDAC9 or HDAC10 did not affect the ability of these cells to express IL-10 mRNA in response to LPS stimulation.”
    Quote in the paperSubstantial claim
  • Findingown data

    Overexpression of HDAC6 enhances IL-10 mRNA expression in LPS-stimulated RAW264.7 cells.

    “Overexpression of HDAC6 (A001723) in RAW264.7 cells, however, was associated with enhanced IL-10 mRNA expression in response to LPS (Fig. 1a).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Findingown data

    In macrophages overexpressing HDAC11, phosphorylation of H3 Ser10 in the proximal Il10 promoter peaks at 30 min but decreases more rapidly than in control.

    “In macrophages overexpressing HDAC11, we found a similar pattern of phosphorylation; the only difference was that after the peak at 30 min, there was a more rapid decrease in this phosphorylation (Fig. 4a).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In HDAC11-overexpressing macrophages, PU.1 binding to the distal Il10 promoter is already increased at time 0 and increases further in response to LPS.

    “In macrophages overexpressing HDAC11, binding of PU.1 to the distal promoter was already increased at time 0 and it increased further in response to LPS (Fig. 4g).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In control macrophages, PU.1 binding to the distal Il10 promoter peaks within 2 h and remains increased for the duration of the analysis.

    “ChIP analysis of the distal promoter region of control macrophages showed that PU.1 binding reached a peak within 2 h and remained increased for the duration of the analysis (Fig. 4g).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In control macrophages, STAT3 binding to the proximal Il10 promoter is evident within 60 min and peaks within 2 h.

    “binding of STAT3 to the proximal region of the Il10 promoter was evident within 60 min of LPS stimulation and reached its peak within 2 h in control macrophages (Fig. 4f)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    HDAC11 is barely detected in the distal Il10 promoter of cells in which HDAC11 expression has been inhibited.

    “HDAC11 was barely detected in the distal Il10 promoter of cells in which HDAC11 expression had been inhibited (Fig. 5h).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In control macrophages, HDAC11 binding to the distal Il10 promoter is detectable 2 h after LPS, is modest, and returns to baseline within 3 h.

    “In control macrophages, changes in HDAC11 were detectable 2 h after LPS stimulation, were modest in magnitude and returned to baseline within 3 h (Fig. 4h).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Disruption of HDAC11 in APCs leads to upregulation of IL-10 expression and impairment of antigen-specific T cell responses.

    “Conversely, disruption of HDAC11 in APCs led to upregulation of expression of the gene encoding IL-10 and impairment of antigen-specific T cell responses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In HDAC11-overexpressing macrophages, HDAC11 binding to the distal Il10 promoter is higher at time 0, peaks within 2 h of LPS, and returns to baseline within 3 h.

    “In macrophages overexpressing HDAC11, there was more binding of this molecule at time 0; it reached its peak within 2 h of LPS stimulation and was followed by a rapid return to baseline within 3 h (Fig. 4h).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overexpression of HDAC11 induces inflammatory APCs that are able to prime naive T cells and restore responsiveness of tolerant CD4+ T cells.

    “Overexpression of HDAC11 inhibited IL-10 expression and induced inflammatory APCs that were able to prime naive T cells and restore the responsiveness of tolerant CD4+ T cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Anti-hemagglutinin CD4+ T cells reisolated from mice exposed to high doses of hemagglutinin peptide had minimal production of IL-2 and lacked IFN-γ production in response to restimulation with hemagglutinin peptide presented by uninfected control PEMs.

    “Indeed, anti-hemagglutinin CD4+ T cells reisolated from these mice had minimal production of IL-2 and lacked IFN-γ production in response to restimulation with hemagglutinin peptide presented by uninfected control PEMs (Fig. 7b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    This early phosphorylation was followed by more acetylation of histones H3 and H4 and subsequent recruitment to the proximal promoter of the transcription factors Sp1 and STAT3.

    “This was followed by more acetylation of histones H3 and H4 and subsequent recruitment to the proximal promoter of the transcription factors Sp1 and STAT3.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although HDAC11 was detected mainly in the distal promoter region, most inhibitory effects on histone acetylation and recruitment of transcription factors occurred in the proximal region of the Il10 promoter.

    “Notably, although we detected HDAC11 mainly in the distal promoter region, most inhibitory effects on histone acetylation and recruitment of transcription factors occurred in the proximal region of the Il10 promoter.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Clonotypic CD4+ T cells encountering antigen in APCs lacking HDAC11 were functionally impaired, producing less IL-2 and lacking IFN-γ production relative to wild-type RAW264.7 cells or RAW264.7 cells transduced with nontargeting shRNA.

    “In contrast to naive CD4+ T cells activated by APCs overexpressing HDAC11 (Fig. 7a), clonotypic CD4+ T cells encountering antigen in APCs lacking HDAC11 were functionally impaired, as they produced less IL-2 and lacked IFN-γ production (Fig. 7c) relative to the clonotypic T cells recognizing cognate antigen on wild-type RAW264.7 cells or RAW264.7 cells transduced with nontargeting shRNA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Genetic manipulation of HDAC11 influenced the inflammatory status of APCs and their ability to determine the functional response of antigen-specific CD4+ T cells.

    “The additional demonstration that genetic manipulation of HDAC11 influenced the inflammatory status of APCs and their ability to determine the functional response of antigen-specific CD4+ T cells indicates that this molecule is a likely target for influencing APC-mediated immune activation versus immune tolerance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    HDAC11 has no known physiological function.

    “HDAC11 is a newly identified member of the HDAC family and thus far no known physiological function for HDAC11 has been demonstrated23.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Gao, L., Cueto, M.A., Asselbergs, F. & Atadja, P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J. Biol. Chem. 277, 25748–25755 (2002). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Phosphorylation of histone H3 at Ser10 is needed for transcriptional activation of the Il10 promoter.

    “Published studies have shown that phosphorylation of histone H3 at the serine residue at position 10 (Ser10) is needed for transcriptional activation of the Il10 promoter24.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Lucas, M., Zhang, X., Prasanna, V. & Mosser, D.M. ERK activation following macrophage FcγR ligation leads to chromatin modifications at the IL-10 locus. J. Immunol. 175, 469–477 (2005). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    PU.1 is a transcription repressor that interacts with the Il10 promoter.

    “PU.1 is a transcription repressor that interacts with the Il10 promoter27,28.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Reuss, E. et al. Differential regulation of interleukin-10 production by genetic and environmental factors - a twin study. Genes Immun. 3, 407–413 (2002). source

      Not checked in the free run.

    • cites [28] Suzuki, M., Yamada, T., Kihara-Negishi, F., Sakurai, T. & Oikawa, T. Direct association between PU.1 and MeCP2 that recruits mSin3A-HDAC complex for PU.1-mediated transcriptional repression. Oncogene 22, 8688–8698 (2003). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Sp1 and STAT3 are transcription factors known to interact with the Il10 promoter.

    “transcription factors known to interact with the Il10 promoter25,26.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Benkhart, E.M., Siedlar, M., Wedel, A., Werner, T. & Ziegler-Heitbrock, H.W. Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression. J. Immunol. 165, 1612–1617 (2000). source

      Not checked in the free run.

    • cites [26] Tone, M., Powell, M.J., Tone, Y., Thompson, S.A.J. & Waldmann, H. IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3. J. Immunol. 165, 286–291 (2000). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Such effect determines the inflammatory status of APCs and influences priming versus tolerance of antigen-specific CD4+ T cells.

    “Such an effect not only determined the inflammatory status of these cells but also influenced priming versus tolerance of antigen-specific CD4+ T cells.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Dynamic changes in the chromatin structure of the Il10 promoter in T cells differentiated into the TH1 or TH2 phenotype closely regulate IL-10 expression.

    “Dynamic changes in the chromatin structure of the Il10 promoter in T cells differentiated into the TH1 or TH2 phenotype closely regulate IL-10 expression32.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Im, S.-H., Hueber, A., Monticelli, S., Kang, K.-H. & Rao, A. Chromatin-level regulation of the IL10 gene in T cells. J. Biol. Chem. 279, 46818–46825 (2004). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All real-time RT-PCR experiments were repeated at least three times with similar results.

    “All real-time RT-PCR experiments were repeated at least three times with similar results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Conformational chromatin changes can regulate the transcription of several genes.

    “In support of that possibility, studies have shown that conformational chromatin changes can regulate the transcription of several genes31.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] West, A.G. & Fraser, P. Remote control of gene transcription. Hum. Mol. Genet. 14, R101–R111 (2005). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In macrophages, more acetylation of the Il10 promoter has been associated with enhanced transcription activity.

    “Similarly, in macrophages, more acetylation of the Il10 promoter has been associated with enhanced transcription activity17.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Zhang, X., Edwards, J.P. & Mosser, D.M. Dynamic and transient remodeling of the macrophage IL-10 promoter during transcription. J. Immunol. 177, 1282–1288 (2006). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Overexpression of HDAC11 in APCs effectively activated naive antigen-specific CD4+ T cells and restored the responsiveness of tolerant T cells, whereas APCs devoid of HDAC11 induced the opposite effect, impairing antigen-specific CD4+ T cell responses.

    “These data collectively indicate that whereas overexpression of HDAC11 in APCs effectively activated naive antigen-specific CD4+ T cells and restored the responsiveness of tolerant T cells, APCs devoid of HDAC11 induced the opposite effect, resulting in impairment of antigen-specific CD4+ T cell responses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All assays were done in triplicate and protein expression was evaluated by immunoblot analysis.

    “All assays were done in triplicate and protein expression was evaluated by immunoblot analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Cells were infected in conditions and with titrations to minimize cellular death and to obtain at least 70-90% of the cell population expressing the protein of interest.

    “Cells were infected in conditions and with titrations to minimize cellular death and to obtain at least 70–90% of the cell population expressing the protein of interest.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The shRNA specific for HDAC11 was a combination of five sequences targeting different segments of HDAC11 mRNA, and the nontargeting control shRNA was a single random sequence not present in the human or mouse genome.

    “The shRNA specific for HDAC11 was a combination of five sequences targeting different segments of HDAC11 mRNA. The nontargeting control shRNA was a single random sequence not present in the human or mouse genome.”
    Quote in the paperNot a substantial claim
27 of 27

  • The paper relies on this without support.

    IL-10 negatively regulates IL-12 expression.

    “Given that IL-10 negatively regulates IL-12 expression, the presence of IL-10 in our experimental system might have masked a potential direct regulatory effect of HDAC11 on Il12 expression.”

  • The paper relies on this without support.

    The in vitro antigen-presentation assays with PEMs and RAW264.7 cells reflect the functional response of antigen-specific CD4+ T cells in vivo.

    “The additional demonstration that genetic manipulation of HDAC11 influenced the inflammatory status of APCs and their ability to determine the functional response of antigen-specific CD4+ T cells indicates that this molecule is a likely target for influencing APC-mediated immune activation versus immune tolerance.”

  • The paper relies on this without support.

    The molecules involved and the sequence of events mediating chromatin modifications of the Il10 promoter are not fully understood.

    “However, the molecules involved and the sequence of events mediating these chromatin modifications are not fully understood.”

  • The paper relies on this without support.

    Little is known about the function of HDAC11 in normal and/or transformed cells.

    “Although there is much information about its structure, enzymatic activity and tissue distribution23,30, little is known about the function of this HDAC in normal and/or transformed cells.”
4 of 4

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?

  • HDAC11 is implicated in immune response cascades and regulates expression of the anti-inflammatory cytokine interleukin 10 (IL-10) by association with HDAC6.

    “Histone deacetylase 11 has been implicated in immune response cascades and shown to regulate the expression of the anti-inflammatory cytokine interleukin 10 (IL-10) by association with HDAC6 (Villagra et al., 2009).”

    From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Villagra et al., 2009

  • HDACs have been implicated in metabolism, inflammation, circadian rhythm, neurological development, and brain function.

    “HDACs have been implicated in diverse biology including metabolism, inflammation, circadian rhythm, as well as neurological development and brain function (Guan et al., 2009; Villagra et al., 2009; Gräff et al., 2012; Jakovcevski and Akbarian, 2012; Falkenberg and Johnstone, 2014; Tough et al., 2016).”

    From Histone deacetylase 11 is an ε-N-Myristoyllysine hydrolase (2018) · cites this paper as Villagra et al., 2009

  • HDAC11 regulates immune tolerance.

    “It has been known for several years that HDAC11 negatively controls IL-10 transcriptional activity in antigen-presenting cells and regulates immune tolerance (Villagra et al., 2009).”

    From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Villagra et al., 2009

  • HDAC11 negatively controls IL-10 transcriptional activity in antigen-presenting cells.

    “It has been known for several years that HDAC11 negatively controls IL-10 transcriptional activity in antigen-presenting cells and regulates immune tolerance (Villagra et al., 2009).”

    From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Villagra et al., 2009

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Authors
Villagra, A., Cheng, F., Wang, H.-W., Suarez, I., Glozak, M., Maurin, M., Nguyen, D., Wright, K. L., Atadja, P. W., Bhalla, K., Pinilla-Ibarz, J., Seto, E., & Sotomayor, E. M.
Affiliations
  • Moffitt Cancer Center (US)
  • University of South Florida (US)
  • Augusta University (US)
Corresponding author
  • Villagra, Alejandro
  • Sotomayor, Eduardo M
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2008-11-16
Volume
10
Issue
1
Pages
92-100
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.1673
PMC
PMC3925685
OpenAlex
W1985845937
Cited by
455
References
39
Citations by year
2026: 21 · 2025: 25 · 2024: 18 · 2023: 17 · 2022: 23 · 2021: 24 · 2020: 30 · 2019: 27 · 2018: 29 · 2017: 28 · 2016: 30 · 2015: 25 · 2014: 23 · 2013: 25 · 2012: 31
FWCI
10.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5k08ca078656-03)
  • National Cancer Institute (R01CA087583, CA78656, R01CA134807, R01CA100850, CA87583)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
HDAC11, histone deacetylase, IL-10, immune tolerance, antigen-presenting cells, T cell activation, T cell tolerance, inflammation, gene expression regulation, autoimmunity, transplantation, cancer immunotherapy
MeSH terms
Animals, Antigen-Presenting Cells, Cell Line, Gene Expression Regulation, Histone Deacetylases, Humans, Immune Tolerance, Lymphocyte Activation, Male, Mice, Inbred BALB C, CD4-Positive T-Lymphocytes, Down-Regulation, Interleukin-10, Mice

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