Osteopontin promotes inflammation in patients with acute coronary syndrome through its activity on IL-17 producing cells.
Atherosclerosis is a progressive disease with a strong inflammatory component. Here we confirm the existence of a critical imbalance in the ratio of Th17 to Treg-cell populations in peripheral CD4(+)  T cells from patients with acute coronary syndrome (ACS), which favors inflammation. This was concurrent with increased IL-17 production from the CD4(+) CD45RA(-) FOXP3(lo)  Treg-cell subset, and elevated osteopontin (OPN) levels in serum from ACS patients. We demonstrate a direct effect of OPN in serum from ACS patients on increased IL-17 production by CD4(+) CD45RA(-) FOXP3(lo)  T cells, mediated through recruitment of the OPN receptors CD29 and CD44, and dependent on STAT3 and the nuclear hormone receptor retinoic-acid-related orphan receptor-γt (RORγt) pathway, but not IL-6 production. To our knowledge and beyond the disease context of ACS, this study constitutes the first demonstration of a critical role for OPN in the positive regulation of inflammation through increased IL-17 production by CD4(+) CD45RA(-) FOXP3(lo)  cells.
Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yingxia
Y
Zheng
Zhihao
Z
Wang
Lin
L
Deng
Xiangliang
X
Yuan
Yanhui
Y
Ma
Guanghui
G
Zhang
Michael P
MP
Gantier
Jun-Ping
JP
Liu
Lisong
L
Shen
Dakang
D
Xu
D054058:Acute Coronary Syndrome / Q000276:immunology*; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D053495:Osteopontin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D015854:Up-Regulation
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; D053495:Osteopontin; D017493:Leukocyte Common Antigens