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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Baudino, Lucie Fossati-jimack, Liliane Sardini, Alessandro Scott, Diane Simpson, Elizabeth Ruseva, Marieta M. Botto, Marina Cook, H. Terence |
| Description | Author Affiliation: Baudino L ( Department of Medicine, Division of Immunology and Inflammation, Centre for Complement and Inflammation Research and Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 0NN, United Kingdom.); |
| Abstract | Apoptotic cells are a source of autoantigens and impairment of their removal contributes to the development of autoimmunity in C1q deficiency. However, the lack of complement component 3 (C3), the predominant complement opsonin, does not predispose to autoimmunity, suggesting a modifying role of C3 in disease pathogenesis. To explore this hypothesis, here we investigated the role of C3 in the T-cell response to apoptotic cell-associated antigens. By comparing the phagosome maturation and the subsequent MHC class II presentation of a peptide derived from the internalized cargo between C3-deficient or C3-sufficient dendritic cells, we found that C3 deficiency accelerated the fusion of the apoptotic cargo with lysosomes. As a result, C3 deficiency led to impaired antigen-specific T-cell proliferation in vitro and in vivo. Notably, preopsonization of the apoptotic cells with C3 activation fragments rectified the trafficking and T-cell stimulation defects. These data indicate that activated C3 may act as a 'chaperone' in the intracellular processing of an apoptotic cargo and, thus, may modulate the T-cell response to self-antigens displayed on dying cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Autoantigens Immunology Complement C3 Metabolism Endocytosis Opsonin Proteins T-Lymphocytes Animals Mice Mice, Knockout Toll-Like Receptor 4 Genetics Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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