IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in Dendritic Cells

Hidemitsu Kitamura, Hokuto Kamon, Shin Ichiro Sawa, Sung Joo Park, Nobuhiko Katunuma, Katsuhiko Ishihara, Masaaki Murakami, Toshio Hirano

Research output: Contribution to journalArticle

137 Citations (Scopus)

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 αβ 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 αβ 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 αβ dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII αβ 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 αβ dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII αβ dimer, Ii, and H2-DM levels in DCs, and suppresses CD4+ T cell-mediated immune responses.

Original languageEnglish
Pages (from-to)491-502
Number of pages12
JournalImmunity
Volume23
Issue number5
DOIs
Publication statusPublished - Nov 1 2005
Externally publishedYes

Fingerprint

cathepsin S
Dendritic Cells
Interleukin-6
Cystatin C
Cathepsins
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in Dendritic Cells. / Kitamura, Hidemitsu; Kamon, Hokuto; Sawa, Shin Ichiro; Park, Sung Joo; Katunuma, Nobuhiko; Ishihara, Katsuhiko; Murakami, Masaaki; Hirano, Toshio.

In: Immunity, Vol. 23, No. 5, 01.11.2005, p. 491-502.

Research output: Contribution to journalArticle

Kitamura, H, Kamon, H, Sawa, SI, Park, SJ, Katunuma, N, Ishihara, K, Murakami, M & Hirano, T 2005, 'IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in Dendritic Cells', Immunity, vol. 23, no. 5, pp. 491-502. https://doi.org/10.1016/j.immuni.2005.09.010
Kitamura, Hidemitsu ; Kamon, Hokuto ; Sawa, Shin Ichiro ; Park, Sung Joo ; Katunuma, Nobuhiko ; Ishihara, Katsuhiko ; Murakami, Masaaki ; Hirano, Toshio. / IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in Dendritic Cells. In: Immunity. 2005 ; Vol. 23, No. 5. pp. 491-502.
@article{608549dc15ef473ca01e80a3468b9b40,
title = "IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in Dendritic Cells",
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 αβ 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 αβ 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 αβ dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII αβ 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 αβ dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII αβ dimer, Ii, and H2-DM levels in DCs, and suppresses CD4+ T cell-mediated immune responses.",
author = "Hidemitsu Kitamura and Hokuto Kamon and Sawa, {Shin Ichiro} and Park, {Sung Joo} and Nobuhiko Katunuma and Katsuhiko Ishihara and Masaaki Murakami and Toshio Hirano",
year = "2005",
month = "11",
day = "1",
doi = "10.1016/j.immuni.2005.09.010",
language = "English",
volume = "23",
pages = "491--502",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - IL-6-STAT3 controls intracellular MHC class II αβ dimer level through cathepsin S activity in Dendritic Cells

AU - Kitamura, Hidemitsu

AU - Kamon, Hokuto

AU - Sawa, Shin Ichiro

AU - Park, Sung Joo

AU - Katunuma, Nobuhiko

AU - Ishihara, Katsuhiko

AU - Murakami, Masaaki

AU - Hirano, Toshio

PY - 2005/11/1

Y1 - 2005/11/1

N2 - 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 αβ 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 αβ 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 αβ dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII αβ 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 αβ dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII αβ dimer, Ii, and H2-DM levels in DCs, and suppresses CD4+ T cell-mediated immune responses.

AB - 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 αβ 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 αβ 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 αβ dimer, Ii, and H2-DM levels in DCs. Cathepsin S overexpression in DCs decreased intracellular MHCII αβ 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 αβ dimer level in DCs. Thus, IL-6-STAT3-mediated increase of cathepsin S activity reduces the MHCII αβ dimer, Ii, and H2-DM levels in DCs, and suppresses CD4+ T cell-mediated immune responses.

UR - http://www.scopus.com/inward/record.url?scp=27744449724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744449724&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2005.09.010

DO - 10.1016/j.immuni.2005.09.010

M3 - Article

C2 - 16286017

AN - SCOPUS:27744449724

VL - 23

SP - 491

EP - 502

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 5

ER -