CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus
Activation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, can lead to hyper-activation of immune cells, including macrophages and DCs, subsequently contributes to the pathogenesis of SLE. CD180, a TLR-like protein, is specifically involved in the development and activat...
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02643/full |
| _version_ | 1818275927572873216 |
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| author | Yonghong Yang Yonghong Yang Cuiling Wang Panpan Cheng Xiaobei Zhang Xuehui Li Yuan Hu Feihong Xu Feng Hong Guanjun Dong Huabao Xiong |
| author_facet | Yonghong Yang Yonghong Yang Cuiling Wang Panpan Cheng Xiaobei Zhang Xuehui Li Yuan Hu Feihong Xu Feng Hong Guanjun Dong Huabao Xiong |
| author_sort | Yonghong Yang |
| collection | DOAJ |
| description | Activation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, can lead to hyper-activation of immune cells, including macrophages and DCs, subsequently contributes to the pathogenesis of SLE. CD180, a TLR-like protein, is specifically involved in the development and activation of immune cells. Our previous study and others have reported that CD180-negative B cells are dramatically increased in SLE patients and responsible for the production of auto-antibodies. However, the mode of CD180 expression on macrophages and DCs in SLE remains unclear and the role of CD180 on regulating TLR7- and TLR9-mediated activation of macrophages and DCs are largely unknown. In the present study, we found that the percentages of CD180-negative macrophages and DCs were both increased in SLE patients and lupus-prone MRL/lpr mice compared with healthy donors and wild-type mice, respectively. Notably, ligation of CD180 significantly inhibited the activation of TLR7 and TLR9 signaling pathways in macrophages and DCs through the Lyn-SHP-1/2 axis. What's more, injection of anti-CD180 Ab could markedly ameliorate the lupus-symptoms of imiquimod-treated mice and lupus-prone MRL/lpr mice through inhibiting the activation of macrophages and DCs. Collectively, our results highlight a critical role of CD180 in regulating TLR7- and TLR9-mediated activation of macrophages and DCs, hinting that CD180 can be regarded as a potential therapeutic target for SLE treatment. |
| first_indexed | 2024-12-12T22:37:32Z |
| format | Article |
| id | doaj.art-4398161509d4478a9c26f6c312cc6850 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T22:37:32Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4398161509d4478a9c26f6c312cc68502022-12-22T00:09:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02643420888CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine LupusYonghong Yang0Yonghong Yang1Cuiling Wang2Panpan Cheng3Xiaobei Zhang4Xuehui Li5Yuan Hu6Feihong Xu7Feng Hong8Guanjun Dong9Huabao Xiong10Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaDepartment of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, ChinaDepartment of Hematology, Affiliated Hospital of Jining Medical University, Jining, ChinaDepartment of Hematology, Affiliated Hospital of Jining Medical University, Jining, ChinaDepartment of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaDepartment of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, ChinaInstitute of Immunology and Molecular Medicine, Jining Medical University, Jining, ChinaDepartment of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesActivation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, can lead to hyper-activation of immune cells, including macrophages and DCs, subsequently contributes to the pathogenesis of SLE. CD180, a TLR-like protein, is specifically involved in the development and activation of immune cells. Our previous study and others have reported that CD180-negative B cells are dramatically increased in SLE patients and responsible for the production of auto-antibodies. However, the mode of CD180 expression on macrophages and DCs in SLE remains unclear and the role of CD180 on regulating TLR7- and TLR9-mediated activation of macrophages and DCs are largely unknown. In the present study, we found that the percentages of CD180-negative macrophages and DCs were both increased in SLE patients and lupus-prone MRL/lpr mice compared with healthy donors and wild-type mice, respectively. Notably, ligation of CD180 significantly inhibited the activation of TLR7 and TLR9 signaling pathways in macrophages and DCs through the Lyn-SHP-1/2 axis. What's more, injection of anti-CD180 Ab could markedly ameliorate the lupus-symptoms of imiquimod-treated mice and lupus-prone MRL/lpr mice through inhibiting the activation of macrophages and DCs. Collectively, our results highlight a critical role of CD180 in regulating TLR7- and TLR9-mediated activation of macrophages and DCs, hinting that CD180 can be regarded as a potential therapeutic target for SLE treatment.https://www.frontiersin.org/article/10.3389/fimmu.2018.02643/fullCD180TLRSLEmacrophageDCs |
| spellingShingle | Yonghong Yang Yonghong Yang Cuiling Wang Panpan Cheng Xiaobei Zhang Xuehui Li Yuan Hu Feihong Xu Feng Hong Guanjun Dong Huabao Xiong CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus Frontiers in Immunology CD180 TLR SLE macrophage DCs |
| title | CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus |
| title_full | CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus |
| title_fullStr | CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus |
| title_full_unstemmed | CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus |
| title_short | CD180 Ligation Inhibits TLR7- and TLR9-Mediated Activation of Macrophages and Dendritic Cells Through the Lyn-SHP-1/2 Axis in Murine Lupus |
| title_sort | cd180 ligation inhibits tlr7 and tlr9 mediated activation of macrophages and dendritic cells through the lyn shp 1 2 axis in murine lupus |
| topic | CD180 TLR SLE macrophage DCs |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02643/full |
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