浆细胞样树突状细胞通过调节 T 细胞的增殖和活性来保护动脉免受粥样硬化。
Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity.
机构信息
Department of Experimental Vascular Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands.
出版信息
Circ Res. 2011 Dec 9;109(12):1387-95. doi: 10.1161/CIRCRESAHA.111.256529. Epub 2011 Oct 20.
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.
背景
与传统树突状细胞不同，浆细胞样树突状细胞（pDC）在抗原呈递方面能力较差，但对 I 型干扰素反应至关重要。尽管有人提出 pDC 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不清楚。
目的
研究 pDC 在动脉粥样硬化中的作用。
方法和结果
我们发现 pDC 在人类动脉粥样硬化病变中几乎不存在，在小鼠斑块中也几乎不存在。令人惊讶的是，用 120G8 mAb 耗尽 pDC 可促进斑块 T 细胞的积累，并加重 LDLr⁻/⁻小鼠的病变发展和进展。pDC 耗竭伴随着 CD4⁺ T 细胞增殖增加、脾 T 细胞表达干扰素-γ以及血浆干扰素-γ水平升高。来自动脉粥样硬化小鼠的淋巴组织 pDC 显示吲哚胺 2,3-双加氧酶（IDO）表达增加，而 IDO 阻断可消除 pDC 对 T 细胞增殖的抑制作用。
结论
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一个有趣靶点。
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