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Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity
Prevention of an immune response against self-antigens derived from apoptotic cells is essential to preclude autoimmune and chronic inflammatory diseases. Here, we describe apoptosis induced externalization of endogenous cytosolic annexin 1 initiating an anti-inflammatory effector mechanism that sup...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640057/ https://www.ncbi.nlm.nih.gov/pubmed/23638088 http://dx.doi.org/10.1371/journal.pone.0062449 |
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author | Weyd, Heiko Abeler-Dörner, Lucie Linke, Björn Mahr, Andrea Jahndel, Veronika Pfrang, Sandra Schnölzer, Martina Falk, Christine S. Krammer, Peter H. |
author_facet | Weyd, Heiko Abeler-Dörner, Lucie Linke, Björn Mahr, Andrea Jahndel, Veronika Pfrang, Sandra Schnölzer, Martina Falk, Christine S. Krammer, Peter H. |
author_sort | Weyd, Heiko |
collection | PubMed |
description | Prevention of an immune response against self-antigens derived from apoptotic cells is essential to preclude autoimmune and chronic inflammatory diseases. Here, we describe apoptosis induced externalization of endogenous cytosolic annexin 1 initiating an anti-inflammatory effector mechanism that suppresses the immune response against antigens of apoptotic cells. Cytosolic annexin 1 rapidly translocated to the apoptotic cell surface and inhibited dendritic cell (DC) activation induced by Toll like receptors (TLR). Annexin 1-inhibited DC showed strongly reduced secretion of pro-inflammatory cytokines (e.g. TNF and IL-12) and costimulatory surface molecules (e.g. CD40 and CD86), while anti-inflammatory mediators like PD-L1 remained unchanged. T cells stimulated by such DC lacked secretion of interferon-γ (IFN-γ) and TNF but retained IL-10 secretion. In mice, annexin 1 prevented the development of inflammatory DC and suppressed the cellular immune response against the model antigen ovalbumin (OVA) expressed in apoptotic cells. Furthermore, annexin 1 on apoptotic cells compromised OVA-specific tumor vaccination and impaired rejection of an OVA-expressing tumor. Thus, our results provide a molecular mechanism for the suppressive activity of apoptotic cells on the immune response towards apoptotic cell-derived self-antigens. This process may play an important role in prevention of autoimmune diseases and of the immune response against cancer. |
format | Online Article Text |
id | pubmed-3640057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36400572013-05-01 Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity Weyd, Heiko Abeler-Dörner, Lucie Linke, Björn Mahr, Andrea Jahndel, Veronika Pfrang, Sandra Schnölzer, Martina Falk, Christine S. Krammer, Peter H. PLoS One Research Article Prevention of an immune response against self-antigens derived from apoptotic cells is essential to preclude autoimmune and chronic inflammatory diseases. Here, we describe apoptosis induced externalization of endogenous cytosolic annexin 1 initiating an anti-inflammatory effector mechanism that suppresses the immune response against antigens of apoptotic cells. Cytosolic annexin 1 rapidly translocated to the apoptotic cell surface and inhibited dendritic cell (DC) activation induced by Toll like receptors (TLR). Annexin 1-inhibited DC showed strongly reduced secretion of pro-inflammatory cytokines (e.g. TNF and IL-12) and costimulatory surface molecules (e.g. CD40 and CD86), while anti-inflammatory mediators like PD-L1 remained unchanged. T cells stimulated by such DC lacked secretion of interferon-γ (IFN-γ) and TNF but retained IL-10 secretion. In mice, annexin 1 prevented the development of inflammatory DC and suppressed the cellular immune response against the model antigen ovalbumin (OVA) expressed in apoptotic cells. Furthermore, annexin 1 on apoptotic cells compromised OVA-specific tumor vaccination and impaired rejection of an OVA-expressing tumor. Thus, our results provide a molecular mechanism for the suppressive activity of apoptotic cells on the immune response towards apoptotic cell-derived self-antigens. This process may play an important role in prevention of autoimmune diseases and of the immune response against cancer. Public Library of Science 2013-04-30 /pmc/articles/PMC3640057/ /pubmed/23638088 http://dx.doi.org/10.1371/journal.pone.0062449 Text en © 2013 Weyd et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Weyd, Heiko Abeler-Dörner, Lucie Linke, Björn Mahr, Andrea Jahndel, Veronika Pfrang, Sandra Schnölzer, Martina Falk, Christine S. Krammer, Peter H. Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity |
title | Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity |
title_full | Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity |
title_fullStr | Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity |
title_full_unstemmed | Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity |
title_short | Annexin A1 on the Surface of Early Apoptotic Cells Suppresses CD8(+) T Cell Immunity |
title_sort | annexin a1 on the surface of early apoptotic cells suppresses cd8(+) t cell immunity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640057/ https://www.ncbi.nlm.nih.gov/pubmed/23638088 http://dx.doi.org/10.1371/journal.pone.0062449 |
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