Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products

Ingrid E. Dumitriu, Paramita Baruah, Barbara Valentinis, Reinhard E. Voll, Martin Herrmann, Peter P. Nawroth, Bernd Arnold, Marco E. Bianchi, Angelo A. Manfredi, Patrizia Rovere-Querini

Research output: Contribution to journalArticle

Abstract

High mobility group box 1 (HMGB1) is an abundant and conserved nuclear protein that is released by necrotic cells and acts in the extracellular environment as a primary proinflammatory signal. In this study we show that human dendritic cells, which are specialized in Ag presentation to T cells, actively release their own HMGB1 into the extracellular milieu upon activation. This secreted HMGB1 is necessary for the up-regulation of CD80, CD83, and CD86 surface markers of human dendritic cells and for IL-12 production. The HMGB1 secreted by dendritic cells is also required for the clonal expansion, survival, and functional polarization of naive T cells. Using neutralizing Abs and receptor for advanced glycation end product-deficient (RAGE-/-) cells, we demonstrate that RAGE is required for the effect of HMGB1 on dendritic cells. HMGB1/RAGE interaction results in downstream activation of MAPKs and NF-κB. The use of an ancient signal of necrosis, HMGB1, by dendritic cells to sustain their own maturation and for activation of T lymphocytes represents a profitable evolutionary mechanism.

Original languageEnglish
Pages (from-to)7506-7515
Number of pages10
JournalJournal of Immunology
Volume174
Issue number12
Publication statusPublished - Jun 15 2005

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ASJC Scopus subject areas

  • Immunology

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