Abstract:
:Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19-CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Roufaiel M,Gracey E,Siu A,Zhu SN,Lau A,Ibrahim H,Althagafi M,Tai K,Hyduk SJ,Cybulsky KO,Ensan S,Li A,Besla R,Becker HM,Xiao H,Luther SA,Inman RD,Robbins CS,Jongstra-Bilen J,Cybulsky MIdoi
10.1038/ni.3564subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1263-1272issue
11eissn
1529-2908issn
1529-2916pii
ni.3564journal_volume
17pub_type
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