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Publication : Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes.

First Author  Manfredi AA Year  2008
Journal  J Immunol Volume  180
Issue  4 Pages  2270-5
PubMed ID  18250435 Mgi Jnum  J:132000
Mgi Id  MGI:3774919 Doi  10.4049/jimmunol.180.4.2270
Citation  Manfredi AA, et al. (2008) Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes. J Immunol 180(4):2270-5
abstractText  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.
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