Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells |
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Authors: | Dumitriu Ingrid E Baruah Paramita Bianchi Marco E Manfredi Angelo A Rovere-Querini Patrizia |
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Institution: | H San Raffaele Scientific Institute, Milan, Italy. |
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Abstract: | 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. |
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Keywords: | Plasmacytoid dendritic cells Cell activation HMGB1 RAGE Immunity |
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