Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells.
Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.
Dumitriu
Ingrid E
IE
H San Raffaele Scientific Institute, Milan, Italy.
Baruah
Paramita
P
Bianchi
Marco E
ME
Manfredi
Angelo A
AA
Rovere-Querini
Patrizia
P
D019898:Autocrine Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D024243:HMGB1 Protein; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors