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. |