TY - JOUR
T1 - Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells
AU - Dumitriu, Ingrid E.
AU - Baruah, Paramita
AU - Bianchi, Marco E.
AU - Manfredi, Angelo A.
AU - Rovere-Querini, Patrizia
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
KW - Cell activation
KW - HMGB1
KW - Immunity
KW - Plasmacytoid dendritic cells
KW - RAGE
UR - http://www.scopus.com/inward/record.url?scp=22544445228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22544445228&partnerID=8YFLogxK
U2 - 10.1002/eji.200526066
DO - 10.1002/eji.200526066
M3 - Article
C2 - 15915542
AN - SCOPUS:22544445228
VL - 35
SP - 2184
EP - 2190
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 7
ER -