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 journalArticlepeer-review

151 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 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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