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Cited by 223Cytokine Signaling Pathways and InteractionsImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

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IL-6-STAT3 Controls Intracellular MHC Class II αβ Dimer Level through Cathepsin S Activity in Dendritic Cells

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Kitamura, Hidemitsu, Kamon, Hokuto, Sawa, Shin-ichiro, Park, Sung-Joo, Katunuma, Nobuhiko, Ishihara, Katsuhiko, Murakami, Masaaki, Hirano, Toshio·2005·Immunity
DOI 10.1016/j.immuni.2005.09.010
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Abstract

We found IL-6-STAT3 pathway suppresses MHC class II (MHCII) expression on dendritic cells (DCs) and attenuates T cell activation. Here, we showed that IL-6-STAT3 signaling reduced intracellular MHCII alphabeta dimmer, Ii, and H2-DM levels in DCs. IL-6-mediated STAT3 activation decreased cystatin C level, an endogenous inhibitor of cathepsins, and enhanced cathepsin activities. Importantly, cathepsin S inhibitors blocked reduction of MHCII alphabeta dimer, Ii, and H2-DM in the IL-6-treated DCs. Overexpression of cystatin C suppressed IL-6-STAT3-mediated increase of cathepsin S activity and reduction of MHCII alphabeta dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII alphabeta dimer, Ii, and H2-DM levels, LPS-mediated surface expression of MHCII and suppressed CD4(+) T cell activation. IL-6-gp130-STAT3 signaling in vivo decreased cystatin C expression and MHCII alphabeta dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII alphabeta dimer, Ii, and H2-DM levels in DCs, and suppresses CD4(+) T cell-mediated immune responses.

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Cited by

Sorted by citations

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Metadata

Authors
Kitamura, H., Kamon, H., Sawa, S.-I., Park, S.-J., Katunuma, N., Ishihara, K., Murakami, M., & Hirano, T.
Affiliations
  • RIKEN (JP)
  • The University of Osaka (JP)
  • Tokushima Bunri University (JP)
Corresponding author
Hirano, Toshio
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2005-11
Volume
23
Issue
5
Pages
491-502
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2005.09.010
OpenAlex
W2074991167
Cited by
223
References
0
Citations by year
2026: 6 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 11 · 2021: 18 · 2020: 13 · 2019: 13 · 2018: 14 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 13 · 2012: 10
FWCI
4.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
IL-6/STAT3 signaling, cathepsin S, dendritic cells, cystatin C, Ii, T cell activation, gp130, LPS, antigen presentation, CD4+ T cells, immunosuppression
MeSH terms
Animals, Histocompatibility Antigens Class II, Cathepsins, Cells, Cultured, Dendritic Cells, Lymphocyte Activation, Mice, Transgenic, RNA, Messenger, Signal Transduction, CD4-Positive T-Lymphocytes, Interleukin-6, Up-Regulation, Cystatins, Dimerization, STAT3 Transcription Factor, Mice

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