Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization.
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.
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Véronique
V
Angeli
Jaime
J
Llodrá
James X
JX
Rong
Kei
K
Satoh
Satoshi
S
Ishii
Takao
T
Shimizu
Edward A
EA
Fisher
Gwendalyn J
GJ
Randolph
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001161:Arteriosclerosis / Q000276:immunology* / Q000503:physiopathology; D002465:Cell Movement / Q000276:immunology*; D008076:Cholesterol, HDL / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000276:immunology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010972:Platelet Activating Factor / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000473:pathology
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D010972:Platelet Activating Factor; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase