Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity.
BACKGROUND
Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type I 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.


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-γ expression by splenic T cells, and plasma interferon-γ 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.
Department of Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands. isabelle.daissormont@maastrichtuniversity.nl
Isabelle T M N
IT
Daissormont
Anette
A
Christ
Lieve
L
Temmerman
Stefan
S
Sampedro Millares
Tom
T
Seijkens
Marco
M
Manca
Mat
M
Rousch
Marjorie
M
Poggi
Louis
L
Boon
Chris
C
van der Loos
Mat
M
Daemen
Esther
E
Lutgens
Bente
B
Halvorsen
Pal
P
Aukrust
Edith
E
Janssen
Erik A L
EA
Biessen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011973:Receptors, LDL; D007371:Interferon-gamma