Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity.

Abstract:

RATIONALE: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. 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-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.

journal_name

Circ Res

journal_title

Circulation research

authors

Daissormont IT,Christ A,Temmerman L,Sampedro Millares S,Seijkens T,Manca M,Rousch M,Poggi M,Boon L,van der Loos C,Daemen M,Lutgens E,Halvorsen B,Aukrust P,Janssen E,Biessen EA

doi

10.1161/CIRCRESAHA.111.256529

subject

Has Abstract

pub_date

2011-12-09 00:00:00

pages

1387-95

issue

12

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.111.256529

journal_volume

109

pub_type

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