Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity.
Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity.
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DOI：
10.1161/circresaha.111.256529
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发表时间：
2011-12-09
影响因子：
20.1
通讯作者：
Biessen EA
中科院分区：
文献类型：
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作者：
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
与传统的树突状细胞（cDC）不同，浆细胞样DC（pDC）的抗原提呈能力较差，对于I型干扰素反应至关重要。虽然被认为存在于人类动脉粥样硬化病变中，但它们在动脉粥样硬化中的作用仍然难以捉摸。探讨pDC在动脉粥样硬化中的作用。我们发现pDC在人类动脉粥样硬化病变中几乎不存在，在小鼠斑块中几乎不存在。令人惊讶的是，在LDLr−/−小鼠中，通过120 G8 mAb给药的pDC消耗促进了斑块T细胞积聚并加剧了病变的发展和进展。PDC消耗伴随着CD 4 + T细胞增殖、脾T细胞IFN-γ表达和血浆IFN-γ水平的增加。来自动脉粥样硬化小鼠的类树突状组织pDC显示吲哚胺2，3-双加氧酶（IDO）表达增加，并且IDO阻断消除了pDC对T细胞增殖的抑制作用。我们的数据揭示了pDC在动脉粥样硬化中的保护作用，可能是通过抑制外周淋巴组织中的T细胞增殖和活性，使pDC成为未来治疗干预的有趣靶点。
Unlike conventional dendritic cells (cDC), plasmacytoid DCs (pDC) are poor in antigen presentation and critical for type I interferon response. While proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive. To investigate the role of pDC in atherosclerosis. 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, IFN-γ expression by splenic T cells and plasma IFN-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. 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.