High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin

D Yang, Q Chen, H Yang, KJ Tracey… - Journal of Leucocyte …, 2007 - academic.oup.com
D Yang, Q Chen, H Yang, KJ Tracey, M Bustin, JJ Oppenheim
Journal of Leucocyte Biology, 2007academic.oup.com
High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays
a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act
as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular
activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and
activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived,
immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs …
Abstract
High mobility group box-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A, B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF-α), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin.
Oxford University Press