TY - JOUR
T1 - Plasmacytoid Dendritic Cells Protect Against Atherosclerosis by Tuning T-Cell Proliferation and Activity
AU - Daissormont, Isabelle T. M. N.
AU - Christ, Anette
AU - Temmerman, Lieve
AU - Sampedro Millares, Stefan
AU - Seijkens, Tom
AU - Rousch, Mat
AU - Poggi, Marjorie
AU - Boon, Louis
AU - van der Loos, Chris
AU - Daemen, Mat
AU - Lutgens, Esther
AU - Halvorsen, Bente
AU - Aukrust, Pal
AU - Janssen, Edith
AU - Biessen, Erik A. L.
PY - 2011
Y1 - 2011
N2 - Rationale: Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type 1 interferon response. Though proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive. Objective: To investigate the role of PDC in atherosclerosis. Methods and Results: We show that PDC are scarcely present in human atherosclerotic lesions and almost absent in mouse plaques. Surprisingly, PDC depletion by 120G8 mAb administration was seen to promote plaque T-cell accumulation and exacerbate lesion development and progression in LDLr(-/-) mice. PDC depletion was accompanied by increased CD4(+) T-cell proliferation, interferon-gamma expression by splenic T cells, and plasma interferon-gamma levels. Lymphoid tissue PDC from atherosclerotic mice showed increased indoleamine 2,3-dioxygenase (IDO) expression and IDO blockage abrogated the PDC suppressive effect on T-cell proliferation. Conclusions: Our data reveal a protective role for PDC in atherosclerosis, possibly by dampening T-cell proliferation and activity in peripheral lymphoid tissue, rendering PDC an interesting target for future therapeutic interventions. (Circ Res. 2011;109:1387-1395.)
AB - Rationale: Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type 1 interferon response. Though proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive. Objective: To investigate the role of PDC in atherosclerosis. Methods and Results: We show that PDC are scarcely present in human atherosclerotic lesions and almost absent in mouse plaques. Surprisingly, PDC depletion by 120G8 mAb administration was seen to promote plaque T-cell accumulation and exacerbate lesion development and progression in LDLr(-/-) mice. PDC depletion was accompanied by increased CD4(+) T-cell proliferation, interferon-gamma expression by splenic T cells, and plasma interferon-gamma levels. Lymphoid tissue PDC from atherosclerotic mice showed increased indoleamine 2,3-dioxygenase (IDO) expression and IDO blockage abrogated the PDC suppressive effect on T-cell proliferation. Conclusions: Our data reveal a protective role for PDC in atherosclerosis, possibly by dampening T-cell proliferation and activity in peripheral lymphoid tissue, rendering PDC an interesting target for future therapeutic interventions. (Circ Res. 2011;109:1387-1395.)
U2 - https://doi.org/10.1161/CIRCRESAHA.111.256529
DO - https://doi.org/10.1161/CIRCRESAHA.111.256529
M3 - Article
C2 - 22021930
SN - 0009-7330
VL - 109
SP - 1387
EP - 1395
JO - Circulation Research
JF - Circulation Research
IS - 12
ER -