Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice
August 25, 2010
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Ovid Technologies (Wolters Kluwer) -American Heart Association
2012
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| Online Access: | http://hdl.handle.net/1721.1/74265 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826201877423849472 |
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| author | Ploegh, Hidde Sun, Jiusong Hartvigsen, Karsten Chou, Meng-Yun Zhang, Yadong Sukhova, Galina K. Zhang, Jie Lopez-Ilasaca, Marco Diehl, Cody J. Yakov, Niva Harats, Dror George, Jacob Witztum, Joseph L. Libby, Peter Shi, Guo-Ping |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ploegh, Hidde Sun, Jiusong Hartvigsen, Karsten Chou, Meng-Yun Zhang, Yadong Sukhova, Galina K. Zhang, Jie Lopez-Ilasaca, Marco Diehl, Cody J. Yakov, Niva Harats, Dror George, Jacob Witztum, Joseph L. Libby, Peter Shi, Guo-Ping |
| author_sort | Ploegh, Hidde |
| collection | MIT |
| description | August 25, 2010 |
| first_indexed | 2024-09-23T11:58:15Z |
| format | Article |
| id | mit-1721.1/74265 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:58:15Z |
| publishDate | 2012 |
| publisher | Ovid Technologies (Wolters Kluwer) -American Heart Association |
| record_format | dspace |
| spelling | mit-1721.1/742652022-09-27T23:09:06Z Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice Ploegh, Hidde Sun, Jiusong Hartvigsen, Karsten Chou, Meng-Yun Zhang, Yadong Sukhova, Galina K. Zhang, Jie Lopez-Ilasaca, Marco Diehl, Cody J. Yakov, Niva Harats, Dror George, Jacob Witztum, Joseph L. Libby, Peter Shi, Guo-Ping Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ploegh, Hidde August 25, 2010 Background: Adaptive immunity and innate immunity play important roles in atherogenesis. Invariant chain (CD74) mediates antigen-presenting cell antigen presentation and T-cell activation. This study tested the hypothesis that CD74-deficient mice have reduced numbers of active T cells and resist atherogenesis. Methods and Results: In low-density lipoprotein receptor–deficient (Ldlr[superscript −/−]) mice, CD74 deficiency (Ldlr[superscript −/−]Cd74[superscript −/−]) significantly reduced atherosclerosis and CD25+-activated T cells in the atheromata. Although Ldlr[superscript −/−]Cd74[superscript −/−] mice had decreased levels of plasma immunoglobulin (Ig) G1, IgG2b, and IgG2c against malondialdehyde-modified LDL (MDA-LDL), presumably as a result of impaired antigen-presenting cell function, Ldlr[superscript −/−]Cd74[superscript −/−] mice showed higher levels of anti–MDA-LDL IgM and IgG3. After immunization with MDA-LDL, Ldlr[superscript −/−]Cd74[superscript −/−] mice had lower levels of all anti–MDA-LDL Ig isotypes compared with Ldlr[superscript −/−] mice. As anticipated, only Ldlr[superscript −/−] splenocytes responded to in vitro stimulation with MDA-LDL, producing Th1/Th2 cytokines. Heat shock protein-65 immunization enhanced atherogenesis in Ldlr[superscript −/−] mice, but Ldlr[superscript −/−] Cd74[superscript −/−] mice remained protected. Compared with Ldlr[superscript −/−] mice, Ldlr[superscript −/−]Cd74[superscript −/−] mice had higher anti–MDA-LDL autoantibody titers, fewer lesion CD25+-activated T cells, impaired release of Th1/Th2 cytokines from antigen-presenting cells after heat shock protein-65 stimulation, and reduced levels of all plasma anti–heat shock protein-65 Ig isotypes. Cytofluorimetry of splenocytes and peritoneal cavity cells of MDA-LDL– or heat shock protein-65–immunized mice showed increased percentages of autoantibody-producing marginal zone B and B-1 cells in Ldlr[superscript −/−]Cd74[superscript −/−] mice compared with Ldlr[superscript −/−] mice. Conclusions: Invariant chain deficiency in Ldlr[superscript −/−] mice reduced atherosclerosis. This finding was associated with an impaired adaptive immune response to disease-specific antigens. Concomitantly, an unexpected increase in the number of innate-like peripheral B-1 cell populations occurred, resulting in increased IgM/IgG3 titers to the oxidation-specific epitopes. 2012-10-25T20:54:32Z 2012-10-25T20:54:32Z 2010-08 2009-07 Article http://purl.org/eprint/type/JournalArticle 0009-7322 1524-4539 http://hdl.handle.net/1721.1/74265 Sun, J. et al. “Deficiency of Antigen-Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice.” Circulation 122.8 (2010): 808–820. https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1161/circulationaha.109.891887 Circulation Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Ovid Technologies (Wolters Kluwer) -American Heart Association PMC |
| spellingShingle | Ploegh, Hidde Sun, Jiusong Hartvigsen, Karsten Chou, Meng-Yun Zhang, Yadong Sukhova, Galina K. Zhang, Jie Lopez-Ilasaca, Marco Diehl, Cody J. Yakov, Niva Harats, Dror George, Jacob Witztum, Joseph L. Libby, Peter Shi, Guo-Ping Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice |
| title | Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice |
| title_full | Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice |
| title_fullStr | Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice |
| title_full_unstemmed | Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice |
| title_short | Deficiency of Antigen Presenting Cell Invariant Chain Reduces Atherosclerosis in Mice |
| title_sort | deficiency of antigen presenting cell invariant chain reduces atherosclerosis in mice |
| url | http://hdl.handle.net/1721.1/74265 https://orcid.org/0000-0002-1090-6071 |
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