sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death
Abstract Soluble glucose regulated protein 78 (sGRP78) has long been suggested as a mediator resolution of inflammation. We previously reported that sGRP78 induced the rapid endocytosis of TLR4 with defective TLR4 signaling. To elucidate the underlying mechanisms, in this study, we investigated how...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05048-5 |
| _version_ | 1811323466392010752 |
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| author | Zhenghao Wu Zhuoshuo Xu Xiaoqi Zhou Heli Li Liang Zhao Yibing Lv Yanyan Guo Guanxin Shen Yong He Ping Lei |
| author_facet | Zhenghao Wu Zhuoshuo Xu Xiaoqi Zhou Heli Li Liang Zhao Yibing Lv Yanyan Guo Guanxin Shen Yong He Ping Lei |
| author_sort | Zhenghao Wu |
| collection | DOAJ |
| description | Abstract Soluble glucose regulated protein 78 (sGRP78) has long been suggested as a mediator resolution of inflammation. We previously reported that sGRP78 induced the rapid endocytosis of TLR4 with defective TLR4 signaling. To elucidate the underlying mechanisms, in this study, we investigated how sGRP78 influenced the behavior and trafficking of TLR4 in myeloid cells. It was found that sGRP78 promoted LPS endocytosis with monomeric TLR4. This internalized monomeric TLR4 formed complexes with p62–LC3, and was degraded in autolysosomes. Furthermore, the sGRP78-enhanced autophagy-dependent TLR4 degradation caused apoptosis and ferroptosis in myeloid cells, contributing to the sGRP78-mediated resolution of inflammation. These reports establish innovative mechanisms for endotoxin clearance and immune regulation by TLR4 degradation, linking innate immunity with multiple ancient processes, including autophagy, apoptosis, and ferroptosis, together through a shared resolution-associated molecular pattern (RAMP)—sGRP78. |
| first_indexed | 2024-04-13T13:55:36Z |
| format | Article |
| id | doaj.art-93074a9bbef240b7b71ff823f9eb18c5 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T13:55:36Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-93074a9bbef240b7b71ff823f9eb18c52022-12-22T02:44:13ZengNature Publishing GroupCell Death and Disease2041-48892022-07-0113711210.1038/s41419-022-05048-5sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell deathZhenghao Wu0Zhuoshuo Xu1Xiaoqi Zhou2Heli Li3Liang Zhao4Yibing Lv5Yanyan Guo6Guanxin Shen7Yong He8Ping Lei9Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Nuclear Medicine and PET Center, Zhongnan Hospital of Wuhan UniversityDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Soluble glucose regulated protein 78 (sGRP78) has long been suggested as a mediator resolution of inflammation. We previously reported that sGRP78 induced the rapid endocytosis of TLR4 with defective TLR4 signaling. To elucidate the underlying mechanisms, in this study, we investigated how sGRP78 influenced the behavior and trafficking of TLR4 in myeloid cells. It was found that sGRP78 promoted LPS endocytosis with monomeric TLR4. This internalized monomeric TLR4 formed complexes with p62–LC3, and was degraded in autolysosomes. Furthermore, the sGRP78-enhanced autophagy-dependent TLR4 degradation caused apoptosis and ferroptosis in myeloid cells, contributing to the sGRP78-mediated resolution of inflammation. These reports establish innovative mechanisms for endotoxin clearance and immune regulation by TLR4 degradation, linking innate immunity with multiple ancient processes, including autophagy, apoptosis, and ferroptosis, together through a shared resolution-associated molecular pattern (RAMP)—sGRP78.https://doi.org/10.1038/s41419-022-05048-5 |
| spellingShingle | Zhenghao Wu Zhuoshuo Xu Xiaoqi Zhou Heli Li Liang Zhao Yibing Lv Yanyan Guo Guanxin Shen Yong He Ping Lei sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death Cell Death and Disease |
| title | sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death |
| title_full | sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death |
| title_fullStr | sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death |
| title_full_unstemmed | sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death |
| title_short | sGRP78 enhances selective autophagy of monomeric TLR4 to regulate myeloid cell death |
| title_sort | sgrp78 enhances selective autophagy of monomeric tlr4 to regulate myeloid cell death |
| url | https://doi.org/10.1038/s41419-022-05048-5 |
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