Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization
Atherosclerosis, an inflammatory progressive vascular disease, causes heart disease and stroke worldwide. B cells with immune suppressive functions have been implicated in autoimmune, inflammatory, and cardiovascular diseases. However, the precise role of regulatory B cells and the interaction with...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-11-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222011398 |
| _version_ | 1797990664846180352 |
|---|---|
| author | Yimin Huang Kongyang Ma Rencai Qin Yaxiong Fang Jingquan Zhou Xiaoyan Dai |
| author_facet | Yimin Huang Kongyang Ma Rencai Qin Yaxiong Fang Jingquan Zhou Xiaoyan Dai |
| author_sort | Yimin Huang |
| collection | DOAJ |
| description | Atherosclerosis, an inflammatory progressive vascular disease, causes heart disease and stroke worldwide. B cells with immune suppressive functions have been implicated in autoimmune, inflammatory, and cardiovascular diseases. However, the precise role of regulatory B cells and the interaction with macrophages in atherosclerosis remains undefined. In our study, eight-week-old female apolipoprotein E null (Apoe−/−) mice were treated with a single dose of vehicle or pristane and then placed on an atherogenic diet for 12 weeks. We found that pristane decreased atherosclerotic lesion formation and increased stability of atherosclerotic plaques in Apoe−/− mice. We also observed lower frequencies of CD19+ B cells but higher frequencies of CD138+ plasma cells and CD206+ M2 macrophages in Apoe−/− mice treated with pristane. Importantly, pristane inhibited immune cell infiltration into the vascular wall. The upregulation of IL-4 in bone-marrow CD138+ plasma cells from pristane-treated Apoe−/− mice was demonstrated by RNA-sequencing (RNA-seq). Consistently, oxidized low-density lipoprotein (oxLDL) directly induced IL-4-secreting plasma cell generation in vitro. In a co-culture system incubating an anti-IL-4 neutralizing antibody, the results showed that oxLDL-induced CD138+ plasma cells could boost M2 macrophage polarization via IL-4 secretion. Our data demonstrate an unexpected role that pristane induces IL-4-producing CD138+ regulatory plasma cell generation and M2 polarization to protect atherosclerosis development. |
| first_indexed | 2024-04-11T08:40:04Z |
| format | Article |
| id | doaj.art-a2c0a96be87f4b3384c03fa8cc482233 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T08:40:04Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-a2c0a96be87f4b3384c03fa8cc4822332022-12-22T04:34:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-11-01155113750Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarizationYimin Huang0Kongyang Ma1Rencai Qin2Yaxiong Fang3Jingquan Zhou4Xiaoyan Dai5Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, ChinaCentre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518107, China; Correspondence authors.Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong 518107, ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, ChinaGuangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, China; Correspondence authors.Atherosclerosis, an inflammatory progressive vascular disease, causes heart disease and stroke worldwide. B cells with immune suppressive functions have been implicated in autoimmune, inflammatory, and cardiovascular diseases. However, the precise role of regulatory B cells and the interaction with macrophages in atherosclerosis remains undefined. In our study, eight-week-old female apolipoprotein E null (Apoe−/−) mice were treated with a single dose of vehicle or pristane and then placed on an atherogenic diet for 12 weeks. We found that pristane decreased atherosclerotic lesion formation and increased stability of atherosclerotic plaques in Apoe−/− mice. We also observed lower frequencies of CD19+ B cells but higher frequencies of CD138+ plasma cells and CD206+ M2 macrophages in Apoe−/− mice treated with pristane. Importantly, pristane inhibited immune cell infiltration into the vascular wall. The upregulation of IL-4 in bone-marrow CD138+ plasma cells from pristane-treated Apoe−/− mice was demonstrated by RNA-sequencing (RNA-seq). Consistently, oxidized low-density lipoprotein (oxLDL) directly induced IL-4-secreting plasma cell generation in vitro. In a co-culture system incubating an anti-IL-4 neutralizing antibody, the results showed that oxLDL-induced CD138+ plasma cells could boost M2 macrophage polarization via IL-4 secretion. Our data demonstrate an unexpected role that pristane induces IL-4-producing CD138+ regulatory plasma cell generation and M2 polarization to protect atherosclerosis development.http://www.sciencedirect.com/science/article/pii/S0753332222011398AtherosclerosisAutoimmunityRegulatory plasma cellMacrophagePolarization |
| spellingShingle | Yimin Huang Kongyang Ma Rencai Qin Yaxiong Fang Jingquan Zhou Xiaoyan Dai Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization Biomedicine & Pharmacotherapy Atherosclerosis Autoimmunity Regulatory plasma cell Macrophage Polarization |
| title | Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization |
| title_full | Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization |
| title_fullStr | Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization |
| title_full_unstemmed | Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization |
| title_short | Pristane attenuates atherosclerosis in Apoe−/− mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization |
| title_sort | pristane attenuates atherosclerosis in apoe mice via il 4 secreting regulatory plasma cell mediated m2 macrophage polarization |
| topic | Atherosclerosis Autoimmunity Regulatory plasma cell Macrophage Polarization |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222011398 |
| work_keys_str_mv | AT yiminhuang pristaneattenuatesatherosclerosisinapoemiceviail4secretingregulatoryplasmacellmediatedm2macrophagepolarization AT kongyangma pristaneattenuatesatherosclerosisinapoemiceviail4secretingregulatoryplasmacellmediatedm2macrophagepolarization AT rencaiqin pristaneattenuatesatherosclerosisinapoemiceviail4secretingregulatoryplasmacellmediatedm2macrophagepolarization AT yaxiongfang pristaneattenuatesatherosclerosisinapoemiceviail4secretingregulatoryplasmacellmediatedm2macrophagepolarization AT jingquanzhou pristaneattenuatesatherosclerosisinapoemiceviail4secretingregulatoryplasmacellmediatedm2macrophagepolarization AT xiaoyandai pristaneattenuatesatherosclerosisinapoemiceviail4secretingregulatoryplasmacellmediatedm2macrophagepolarization |