Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6 - STAT3 signaling pathway

Siyuan Liang, Vladimir Ristich, Hisashi Arase, Jean Dausset, Edgardo D. Carosella, Anatolij Horuzsko

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The expression of Ig-like transcript (ILT) inhibitory receptors is a characteristic of tolerogenic dendritic cells (DCs). However, the mechanisms of modulation of DCs via ILT receptors remain poorly defined. HLA-G is a preferential ligand for several ILTs. Recently, we demonstrated that triggering of ILT4 by HLA-G1 inhibits maturation of human monocyte-derived conventional DCs and murine DCs from ILT4 transgenic mice, resulting in diminished expression of MHC class II molecules, CD80 and CD86 costimulatory molecules, and prolongation of skin allograft survival. Different isoforms of HLA-G have diverse effects on the efficiency to induce ILT-mediated signaling. In this work, we show that HLA-G1 tetrameric complex and HLA-G5 dimer, but not HLA-G5 monomer, induce strong ILT-mediated signaling. We determined that the arrest of maturation of ILT4-positive DCs by HLA-G ligands involves the IL-6 signaling pathway and STAT3 activation. Ligation of ILT4 with HLA-G on DCs results in recruitment of SHP-1 and SHP-2 protein tyrosine phosphatases. We propose a model where SHP-2 and the IL-6-STAT3 signaling pathway play critical roles in the modulation of DC differentiation by ILT4 and HLA-G.

Original languageEnglish (US)
Pages (from-to)8357-8362
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number24
DOIs
StatePublished - Jun 17 2008

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HLA-G Antigens
Dendritic Cells
Cell Differentiation
Interleukin-6
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Ligands
Critical Pathways
Transgenic Mice
Allografts
Ligation
Monocytes
Protein Isoforms

Keywords

  • Immunomodulation
  • Inhibitory receptor

ASJC Scopus subject areas

  • General

Cite this

Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6 - STAT3 signaling pathway. / Liang, Siyuan; Ristich, Vladimir; Arase, Hisashi; Dausset, Jean; Carosella, Edgardo D.; Horuzsko, Anatolij.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 24, 17.06.2008, p. 8357-8362.

Research output: Contribution to journalArticle

Liang, Siyuan ; Ristich, Vladimir ; Arase, Hisashi ; Dausset, Jean ; Carosella, Edgardo D. ; Horuzsko, Anatolij. / Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6 - STAT3 signaling pathway. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 24. pp. 8357-8362.
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