TY - JOUR
T1 - Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization
AU - Angeli, Véronique
AU - Llodrá, Jaime
AU - Rong, James X.
AU - Satoh, Kei
AU - Ishii, Satoshi
AU - Shimizu, Takao
AU - Fisher, Edward A.
AU - Randolph, Gwendalyn J.
N1 - Funding Information:
We thank Andrew Assee for assistance with preliminary experiments, Dr. Diana M. Stafforini (University of Utah) and Dr. Takehiko Yokomizo (University of Tokyo) for advice, and Dr. Miriam Merad for critical reading of the manuscript. We also thank Dr. Thomas Dudler (ICOS Corporation) and Dr. Sem Saeland (Schering Plough) for provision of recombinant PAFAH and anti-langerin mAb, respectively. This work was supported by National Institutes of Health grants HL69446 and AI49653 to G.J.R. and HL61814 to E.A.F. Studies on Pafr −/− mice included support by grants-in-aid from the Ministry of Education, Science, Culture, Sports and Technology and the Ministry of Health, Labor, and Welfare of Japan (S.I. and T.S.). V.A. was supported by a postdoctoral fellowship from the European Molecular Biology Organization.
PY - 2004/10
Y1 - 2004/10
N2 - High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells (DCs) locally, promoted dermal inflammation, and induced lymph node hypertrophy. Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming. Impaired migration resulted from inhibitory signals generated by platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic. Normal DC migration and priming was restored by HDL or HDL-associated PAF acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL. Thus, atherosclerotic changes can sequester activated DCs in the periphery where they may aggravate local inflammation even as they poorly carry out functions that require their migration to lymph nodes. In this context, HDL and PAFAH maintain a normally functional DC compartment.
AB - High LDL and/or low HDL are risk factors for atherosclerosis and are also a common clinical feature in systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. Here, we show that changes in lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells (DCs) locally, promoted dermal inflammation, and induced lymph node hypertrophy. Paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming. Impaired migration resulted from inhibitory signals generated by platelet-activating factor (PAF) or oxidized LDL that acts as a PAF mimetic. Normal DC migration and priming was restored by HDL or HDL-associated PAF acetylhydrolase (PAFAH), which mediates inactivation of PAF and oxidized LDL. Thus, atherosclerotic changes can sequester activated DCs in the periphery where they may aggravate local inflammation even as they poorly carry out functions that require their migration to lymph nodes. In this context, HDL and PAFAH maintain a normally functional DC compartment.
UR - http://www.scopus.com/inward/record.url?scp=5644273775&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2004.09.003
DO - 10.1016/j.immuni.2004.09.003
M3 - Article
C2 - 15485633
AN - SCOPUS:5644273775
SN - 1074-7613
VL - 21
SP - 561
EP - 574
JO - Immunity
JF - Immunity
IS - 4
ER -