Plasmacytoid Dendritic Cells Protect Against Atherosclerosis by Tuning T-Cell Proliferation and Activity

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.