Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity.
| Autor: | Daissormont IT; Department of Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands. isabelle.daissormont@maastrichtuniversity.nl, 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 |
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| Jazyk: | angličtina |
| Zdroj: | Circulation research [Circ Res] 2011 Dec 09; Vol. 109 (12), pp. 1387-95. Date of Electronic Publication: 2011 Oct 20. |
| DOI: | 10.1161/CIRCRESAHA.111.256529 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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