Graebner, Rolf and Loetzer, Katharina and Doepping, Sandra and Hildner, Markus and Radke, Doerte and Beer, Michael and Spanbroek, Rainer and Lippert, Beatrix and Reardon, Catherine A. and Getz, Godfrey S. and Fu, Yang-Xin and Hehlgans, Thomas and Mebius, Reina E. and van der Wall, Michael and Kruspe, Dagmar and Englert, Christoph and Lovas, Agnes and Hu, Desheng and Randolph, Gwendalyn J. and Weih, Falk and Habenicht, Andreas J. R. (2009) Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE(-/-) mice. JOURNAL OF EXPERIMENTAL MEDICINE, 206 (1). pp. 233-248. ISSN 0022-1007,
Full text not available from this repository. (Request a copy)Abstract
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 beta receptor (LT beta R) 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 LT beta R-Ig to interrupt LT beta R signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LT beta R pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FOLLICULAR DENDRITIC CELLS; SMOOTH-MUSCLE-CELLS; REGULATORY T-CELLS; E-DEFICIENT MICE; B-CELLS; LASER MICRODISSECTION; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; ORGAN DEVELOPMENT; IMMUNE-RESPONSES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Oct 2020 09:09 |
| Last Modified: | 07 Oct 2020 09:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29573 |
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