FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells
The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not...
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| Format: | Article |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01424/full |
| _version_ | 1811239389976592384 |
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| author | Yi-Gen Pan Yen-Ling Yu Chi-Chien Lin Lewis L. Lanier Lewis L. Lanier Ching-Liang Chu |
| author_facet | Yi-Gen Pan Yen-Ling Yu Chi-Chien Lin Lewis L. Lanier Lewis L. Lanier Ching-Liang Chu |
| author_sort | Yi-Gen Pan |
| collection | DOAJ |
| description | The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes. In addition, increments of T cell activation and T helper 17 polarization induced by FcRγ-deficient DCs were observed both in vitro and in vivo. Examining the Dectin-1 signaling, we revealed that the activations of several signaling molecules were augmented in FcRγ-deficient DCs stimulated with Dectin-1 ligands. Furthermore, we demonstrated that the association of phosphatases SHP-1 and PTEN with FcRγ may contribute to the negative regulation of FcRγ in Dectin-1 activation in DCs. These results extend the inhibitory effect of ITAM-containing adapters to Dectin-1 response in immune functions, even though Dectin-1 contains an ITAM-like intracellular domain. According to the role of Dectin-1 in responding to microbes and tumor cells, our finding may have applications in the development of vaccine and cancer therapy. |
| first_indexed | 2024-04-12T12:59:09Z |
| format | Article |
| id | doaj.art-4ec0dfa9a3ea458f83cbb6b2fdc17b7a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T12:59:09Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4ec0dfa9a3ea458f83cbb6b2fdc17b7a2022-12-22T03:32:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01424297396FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic CellsYi-Gen Pan0Yen-Ling Yu1Chi-Chien Lin2Lewis L. Lanier3Lewis L. Lanier4Ching-Liang Chu5Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, TaiwanInstitute of Biomedical Sciences, National Chung Hsin University, Taichung, TaiwanDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, United StatesThe Parker Institute for Cancer Immunotherapy, University of California San Francisco, San Francisco, CA, United StatesGraduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, TaiwanThe inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes. In addition, increments of T cell activation and T helper 17 polarization induced by FcRγ-deficient DCs were observed both in vitro and in vivo. Examining the Dectin-1 signaling, we revealed that the activations of several signaling molecules were augmented in FcRγ-deficient DCs stimulated with Dectin-1 ligands. Furthermore, we demonstrated that the association of phosphatases SHP-1 and PTEN with FcRγ may contribute to the negative regulation of FcRγ in Dectin-1 activation in DCs. These results extend the inhibitory effect of ITAM-containing adapters to Dectin-1 response in immune functions, even though Dectin-1 contains an ITAM-like intracellular domain. According to the role of Dectin-1 in responding to microbes and tumor cells, our finding may have applications in the development of vaccine and cancer therapy.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01424/fullFcεRI γ-chainDAP12dendritic cellDectin-1immunoreceptor tyrosine-based activation motifSHP-1 |
| spellingShingle | Yi-Gen Pan Yen-Ling Yu Chi-Chien Lin Lewis L. Lanier Lewis L. Lanier Ching-Liang Chu FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells Frontiers in Immunology FcεRI γ-chain DAP12 dendritic cell Dectin-1 immunoreceptor tyrosine-based activation motif SHP-1 |
| title | FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells |
| title_full | FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells |
| title_fullStr | FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells |
| title_full_unstemmed | FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells |
| title_short | FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells |
| title_sort | fcεri γ chain negatively modulates dectin 1 responses in dendritic cells |
| topic | FcεRI γ-chain DAP12 dendritic cell Dectin-1 immunoreceptor tyrosine-based activation motif SHP-1 |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01424/full |
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