Dumitriu Ingrid E, Baruah Paramita, Bianchi Marco E, Manfredi Angelo A, Rovere-Querini Patrizia
H San Raffaele Scientific Institute, Milan, Italy.
Eur J Immunol. 2005 Jul;35(7):2184-90. doi: 10.1002/eji.200526066.
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.
树突状细胞（DC）是先天性和适应性免疫反应的关键组成部分。浆细胞样DC（pDC）是一种特殊的DC亚群，可响应微生物产生大量I型干扰素。高迁移率族蛋白B1（HMGB1）是一种丰富的核蛋白，当在细胞外释放时，它作为一种有效的促炎因子发挥作用。我们发现，TLR9激活后，HMGB1离开成熟pDC的细胞核，并且pDC在质膜上表达HMGB1的特征最明确的受体RAGE。当HMGB1/RAGE途径被破坏时，pDC的成熟和I型干扰素分泌受到阻碍。这些结果揭示了HMGB1和RAGE是第一个已知的调节pDC成熟的自分泌环，并表明HMGB1/RAGE的拮抗剂可能具有治疗人类全身性疾病的潜力。
