Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell.
Cell surface CD47 interacts with its receptor, signal-regulatory-protein α (SIRPα) that is expressed predominantly on macrophages, to inhibit phagocytosis of normal, healthy cells. This "don't eat me" signal is mediated through tyrosine phosphorylation of SIRPα at the cytoplasmic ITIM...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3779186?pdf=render |
| _version_ | 1819011363435970560 |
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| author | Natan Toledano Devorah Gur-Wahnon Adi Ben-Yehuda Jacob Rachmilewitz |
| author_facet | Natan Toledano Devorah Gur-Wahnon Adi Ben-Yehuda Jacob Rachmilewitz |
| author_sort | Natan Toledano |
| collection | DOAJ |
| description | Cell surface CD47 interacts with its receptor, signal-regulatory-protein α (SIRPα) that is expressed predominantly on macrophages, to inhibit phagocytosis of normal, healthy cells. This "don't eat me" signal is mediated through tyrosine phosphorylation of SIRPα at the cytoplasmic ITIM motifs and the recruitment of the phosphatase, SHP-1. We previously revealed a novel mechanism for the activation of the STAT3 pathway and the regulation of human APC maturation and function that is based on cell:cell interaction. In this study, we present evidence supporting the notion that CD47:SIRPα serves as a cell surface receptor: ligand pair involved in this contact-dependent STAT3 activation and regulation of APC maturation. We show that upon co-culturing APC with various primary and tumor cell lines STAT3 phosphorylation and IL-10 expression are induced, and such regulation could be suppressed by specific CD47 siRNAs and shRNAs. Significantly, >50% reduction in CD47 expression abolished the contact-dependent inhibition of T cell activation. Furthermore, co-immunoprecipitation experiments revealed a physical association between SIRPα and STAT3. Thus, we suggest that in addition to signaling through the ITIM-SHP-1 complex that transmit an anti-phagocytotic, CD47:SIRPα also triggers STAT3 signaling that is linked to an immature APC phenotype and peripheral tolerance under steady state and pathological conditions. |
| first_indexed | 2024-12-21T01:26:58Z |
| format | Article |
| id | doaj.art-1a68f5e8283d4ec3b36a8b825020386f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:26:58Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1a68f5e8283d4ec3b36a8b825020386f2022-12-21T19:20:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7559510.1371/journal.pone.0075595Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell.Natan ToledanoDevorah Gur-WahnonAdi Ben-YehudaJacob RachmilewitzCell surface CD47 interacts with its receptor, signal-regulatory-protein α (SIRPα) that is expressed predominantly on macrophages, to inhibit phagocytosis of normal, healthy cells. This "don't eat me" signal is mediated through tyrosine phosphorylation of SIRPα at the cytoplasmic ITIM motifs and the recruitment of the phosphatase, SHP-1. We previously revealed a novel mechanism for the activation of the STAT3 pathway and the regulation of human APC maturation and function that is based on cell:cell interaction. In this study, we present evidence supporting the notion that CD47:SIRPα serves as a cell surface receptor: ligand pair involved in this contact-dependent STAT3 activation and regulation of APC maturation. We show that upon co-culturing APC with various primary and tumor cell lines STAT3 phosphorylation and IL-10 expression are induced, and such regulation could be suppressed by specific CD47 siRNAs and shRNAs. Significantly, >50% reduction in CD47 expression abolished the contact-dependent inhibition of T cell activation. Furthermore, co-immunoprecipitation experiments revealed a physical association between SIRPα and STAT3. Thus, we suggest that in addition to signaling through the ITIM-SHP-1 complex that transmit an anti-phagocytotic, CD47:SIRPα also triggers STAT3 signaling that is linked to an immature APC phenotype and peripheral tolerance under steady state and pathological conditions.http://europepmc.org/articles/PMC3779186?pdf=render |
| spellingShingle | Natan Toledano Devorah Gur-Wahnon Adi Ben-Yehuda Jacob Rachmilewitz Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell. PLoS ONE |
| title | Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell. |
| title_full | Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell. |
| title_fullStr | Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell. |
| title_full_unstemmed | Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell. |
| title_short | Novel CD47: SIRPα dependent mechanism for the activation of STAT3 in antigen-presenting cell. |
| title_sort | novel cd47 sirpα dependent mechanism for the activation of stat3 in antigen presenting cell |
| url | http://europepmc.org/articles/PMC3779186?pdf=render |
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