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Angelo A Manfredi, Annalisa Capobianco, Antonio Esposito, Francesco De Cobelli, Tamara Canu, Antonella Monno, Angela Raucci, Francesca Sanvito, Claudio Doglioni, Peter P Nawroth, Angelika Bierhaus, Marco E Bianchi, Patrizia Rovere-Querini, Alessandro Del Maschio, Maturing Dendritic Cells Depend on RAGE for In Vivo Homing to Lymph Nodes, The Journal of Immunology, Volume 180, Issue 4, February 2008, Pages 2270–2275, https://doi.org/10.4049/jimmunol.180.4.2270
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Abstract
The mobilization of dendritic cells (DCs) from peripheral tissues is critical for the establishment of T cell-dependent immune responses or tolerance, because the physical interaction of DCs with naive T cells takes place in the T cell areas of lymph nodes. The autocrine/paracrine release of the high mobility group box 1 (HMGB1) nuclear protein by DCs controls the outcome of the DC–T cell interaction, influencing the priming/Th1 polarization of naive T cells. We herein present evidence that the receptor for advanced glycation end products (RAGE), a multiligand member of the Ig superfamily of cell-surface molecules that acts as a receptor for HMGB1, plays a nonredundant role in DC homing to lymph nodes. We used noninvasive imaging by magnetic resonance and immunohistochemistry to track DCs after s.c. injection in the footpad of wild-type+/+ or RAGE−/− mice. Maturing DCs expressing RAGE effectively migrated in both conditions. In contrast, RAGE−/− DCs failed to reach the draining popliteal lymph nodes of +/+ and −/− mice, indicating that the integrity of RAGE is required for DC mobilization. Thus the HMGB1-RAGE pathway is a checkpoint in DC maturation and function and a candidate for targeted therapies.