Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice.
Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice.
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DOI：
10.1084/jem.20080752
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发表时间：
2009-01-16
期刊：
影响因子：
--
通讯作者：
Habenicht AJ
中科院分区：
文献类型：
--
作者：
Gräbner R;Lötzer K;Döpping S;Hildner M;Radke D;Beer M;Spanbroek R;Lippert B;Reardon CA;Getz GS;Fu YX;Hehlgans T;Mebius RE;van der Wall M;Kruspe D;Englert C;Lovas A;Hu D;Randolph GJ;Weih F;Habenicht AJ
动脉粥样硬化涉及主动脉内膜中富含巨噬细胞的炎症。越来越多的人认识到，这种内膜炎症随着时间的推移会被邻近外膜的明显炎症反应所掩盖。尽管内膜和外膜中协调的炎症灶之间的串扰似乎是隐含的，但其通信的机制尚不清楚。在这里，使用详细的成像分析，微阵列分析，激光捕获显微切割，过继淋巴细胞转移，和功能阻断研究，我们承诺，以确定这一机制。我们发现，在老年apoE−/−小鼠中，腹主动脉内膜斑块下的中膜平滑肌细胞（SMC）通过光敏素β受体（LTβR）被激活，表达淋巴器官趋化因子CXCL 13和CCL 21。这些信号反过来触发了精心制作的真实的主动脉外膜三级淋巴器官（ATLO）的发育，这些器官包含功能性管道网、B细胞滤泡内的生发中心、浆细胞簇、T细胞区域中的高内皮微静脉（HEV）和高比例的T调节细胞。用LTβR-Ig阻断SMC中LTβR信号传导的apoE−/−小鼠治疗强烈降低了HEV丰度、CXCL 13和CCL 21表达，并破坏了ATLO的结构和维持。因此，LTβR通路在形成动脉壁的免疫学特征和整体完整性方面具有重要作用。
Atherosclerosis involves a macrophage-rich inflammation in the aortic intima. It is increasingly recognized that this intimal inflammation is paralleled over time by a distinct inflammatory reaction in adjacent adventitia. Though cross talk between the coordinated inflammatory foci in the intima and the adventitia seems implicit, the mechanism(s) underlying their communication is unclear. Here, using detailed imaging analysis, microarray analyses, laser-capture microdissection, adoptive lymphocyte transfers, and functional blocking studies, we undertook to identify this mechanism. We show that in aged apoE−/− mice, medial smooth muscle cells (SMCs) beneath intimal plaques in abdominal aortae become activated through lymphotoxin β receptor (LTβR) to express the lymphorganogenic chemokines CXCL13 and CCL21. These signals in turn trigger the development of elaborate bona fide adventitial aortic tertiary lymphoid organs (ATLOs) containing functional conduit meshworks, germinal centers within B cell follicles, clusters of plasma cells, high endothelial venules (HEVs) in T cell areas, and a high proportion of T regulatory cells. Treatment of apoE−/− mice with LTβR-Ig to interrupt LTβR signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LTβR pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall.
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影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
异位LT Alphaββ指导淋巴器官新生成，并具有外周节点地址和HEV限制的磺胺转移酶的表达。
DOI：
10.1084/jem.20021761
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Drayton DL;Ying X;Lee J;Lesslauer W;Ruddle NH
通讯作者：
Ruddle NH
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
82.9
作者：
Ait-Oufella, H;Salomon, BL;Mallat, Z
通讯作者：
Mallat, Z
DOI：
10.1073/pnas.0606697104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Furtado, Glaucia C.;Marinkovic, Tatjana;Lira, Sergio A.
通讯作者：
Lira, Sergio A.