Essential role of DAP12 signaling in macrophage programming into a fusion-competent state.
Multinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (T...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797054590338727936 |
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| author | Helming, L Tomasello, E Kyriakides, T Martinez, F Takai, T Gordon, S Vivier, E |
| author_facet | Helming, L Tomasello, E Kyriakides, T Martinez, F Takai, T Gordon, S Vivier, E |
| author_sort | Helming, L |
| collection | OXFORD |
| description | Multinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (TREM-2), and the downstream protein tyrosine kinase Syk is required for the cytokine-induced formation of giant cells and that overexpression of DAP12 potentiates macrophage fusion. We also present evidence that DAP12 is a general macrophage fusion regulator and is involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DC-STAMP and Cadherin 1. Thus, DAP12 is involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state. |
| first_indexed | 2024-03-06T18:59:21Z |
| format | Journal article |
| id | oxford-uuid:12f9ad62-ab63-4eb3-9e52-ce4875daa421 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:59:21Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:12f9ad62-ab63-4eb3-9e52-ce4875daa4212022-03-26T10:11:11ZEssential role of DAP12 signaling in macrophage programming into a fusion-competent state.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:12f9ad62-ab63-4eb3-9e52-ce4875daa421EnglishSymplectic Elements at Oxford2008Helming, LTomasello, EKyriakides, TMartinez, FTakai, TGordon, SVivier, EMultinucleated giant cells, formed by fusion of macrophages, are a hallmark of granulomatous inflammation. With a genetic approach, we show that signaling through the adaptor protein DAP12 (DNAX activating protein of 12 kD), its associated receptor triggering receptor expressed by myeloid cells 2 (TREM-2), and the downstream protein tyrosine kinase Syk is required for the cytokine-induced formation of giant cells and that overexpression of DAP12 potentiates macrophage fusion. We also present evidence that DAP12 is a general macrophage fusion regulator and is involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DC-STAMP and Cadherin 1. Thus, DAP12 is involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state. |
| spellingShingle | Helming, L Tomasello, E Kyriakides, T Martinez, F Takai, T Gordon, S Vivier, E Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. |
| title | Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. |
| title_full | Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. |
| title_fullStr | Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. |
| title_full_unstemmed | Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. |
| title_short | Essential role of DAP12 signaling in macrophage programming into a fusion-competent state. |
| title_sort | essential role of dap12 signaling in macrophage programming into a fusion competent state |
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