Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice
Interleukin- (IL-) 35, a novel functional cytokine of regulatory T cells (Treg) comprised of the IL-12p35 subunit and the other subunit Epstein-Barr virus-induced gene 3 (EBI3), regulates the activity of CD4+ T cells and macrophages, thereby playing a critical role in inflammatory and autoimmune dis...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/3152040 |
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| author | Ying Huang Haiying Hu Ling Liu Jing Ye Zhen Wang Bin Que Wenjing Liu Ying Shi Tao Zeng Lei Shi Qingwei Ji Chao Chang Yingzhong Lin |
| author_facet | Ying Huang Haiying Hu Ling Liu Jing Ye Zhen Wang Bin Que Wenjing Liu Ying Shi Tao Zeng Lei Shi Qingwei Ji Chao Chang Yingzhong Lin |
| author_sort | Ying Huang |
| collection | DOAJ |
| description | Interleukin- (IL-) 35, a novel functional cytokine of regulatory T cells (Treg) comprised of the IL-12p35 subunit and the other subunit Epstein-Barr virus-induced gene 3 (EBI3), regulates the activity of CD4+ T cells and macrophages, thereby playing a critical role in inflammatory and autoimmune diseases. Previous studies demonstrated that both recombinant mice and human IL-35 attenuated atherosclerosis in ApoE-/- mice. Additionally, EBI3 deficiency enhanced the activation of macrophages and increased atherosclerotic lesions in LDLR-/- mice. This study generated double-deficient mice for ApoE and IL-12p35 (ApoE-/- IL-12p35-/- mice) and investigated the effect of IL-12p35 deficiency on atherosclerosis. IL-12p35 deficiency alleviated Th1/Th2 imbalance, aggravated Th17/Treg imbalance, and attenuated atherosclerotic plaque formation in ApoE-/- mice. Additionally, exogenous rIL-35 treatment reversed the imbalance of Th17/Treg and attenuated atherosclerosis in ApoE-/- mice. These findings suggest that IL-12p35 deficiency ameliorates atherosclerosis in ApoE-/- mice, partially, via attenuating the Th1/Th2 imbalance, although IL-12p35 deficiency aggravates the Th17/Treg imbalance. |
| format | Article |
| id | doaj-art-d80770a8770a448aaea1414993631d55 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-d80770a8770a448aaea1414993631d552025-02-03T01:07:20ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/31520403152040Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- MiceYing Huang0Haiying Hu1Ling Liu2Jing Ye3Zhen Wang4Bin Que5Wenjing Liu6Ying Shi7Tao Zeng8Lei Shi9Qingwei Ji10Chao Chang11Yingzhong Lin12Department of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, Handan First Hospital, Handan 056002, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaEmergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, ChinaDepartment of Cardiology, Handan First Hospital, Handan 056002, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Cardiology, Handan First Hospital, Handan 056002, ChinaDepartment of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaInterleukin- (IL-) 35, a novel functional cytokine of regulatory T cells (Treg) comprised of the IL-12p35 subunit and the other subunit Epstein-Barr virus-induced gene 3 (EBI3), regulates the activity of CD4+ T cells and macrophages, thereby playing a critical role in inflammatory and autoimmune diseases. Previous studies demonstrated that both recombinant mice and human IL-35 attenuated atherosclerosis in ApoE-/- mice. Additionally, EBI3 deficiency enhanced the activation of macrophages and increased atherosclerotic lesions in LDLR-/- mice. This study generated double-deficient mice for ApoE and IL-12p35 (ApoE-/- IL-12p35-/- mice) and investigated the effect of IL-12p35 deficiency on atherosclerosis. IL-12p35 deficiency alleviated Th1/Th2 imbalance, aggravated Th17/Treg imbalance, and attenuated atherosclerotic plaque formation in ApoE-/- mice. Additionally, exogenous rIL-35 treatment reversed the imbalance of Th17/Treg and attenuated atherosclerosis in ApoE-/- mice. These findings suggest that IL-12p35 deficiency ameliorates atherosclerosis in ApoE-/- mice, partially, via attenuating the Th1/Th2 imbalance, although IL-12p35 deficiency aggravates the Th17/Treg imbalance.http://dx.doi.org/10.1155/2019/3152040 |
| spellingShingle | Ying Huang Haiying Hu Ling Liu Jing Ye Zhen Wang Bin Que Wenjing Liu Ying Shi Tao Zeng Lei Shi Qingwei Ji Chao Chang Yingzhong Lin Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice Mediators of Inflammation |
| title | Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice |
| title_full | Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice |
| title_fullStr | Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice |
| title_full_unstemmed | Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice |
| title_short | Interleukin-12p35 Deficiency Reverses the Th1/Th2 Imbalance, Aggravates the Th17/Treg Imbalance, and Ameliorates Atherosclerosis in ApoE-/- Mice |
| title_sort | interleukin 12p35 deficiency reverses the th1 th2 imbalance aggravates the th17 treg imbalance and ameliorates atherosclerosis in apoe mice |
| url | http://dx.doi.org/10.1155/2019/3152040 |
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