<i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis
Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in <i>Per1/Per2</i&g...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/21/12962 |
| _version_ | 1797467961130221568 |
|---|---|
| author | Ruyi He Shijie Zhang Jiale Yu Xiaojie Yu Jian Wang Yi Qiu Wenting Zhou Fangyi Wang Feng Ren Zhiguo Liu |
| author_facet | Ruyi He Shijie Zhang Jiale Yu Xiaojie Yu Jian Wang Yi Qiu Wenting Zhou Fangyi Wang Feng Ren Zhiguo Liu |
| author_sort | Ruyi He |
| collection | DOAJ |
| description | Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in <i>Per1/Per2</i> double-knockout (DKO) and wild-type (WT) mice aged 4, 9, and 14 months. Compared to the WT mice, the DKO mice had smaller spleen white pulp (WP) and lymphocyte germinal area, as well as fewer immune cells with age—these differences were especially clear. The spleen lymphocyte mortality, malondialdehyde (MDA) levels, reactive oxygen species (ROS) levels, and ferritin-binding receptor (TFR1) levels were significantly higher in the 14-month-old DKO mice than in WT mice of the same age. Transcriptome analysis showed that most of the differentially expressed mRNAs were enriched in DNA damage repair-related pathways. In DKO mice, spleen cells showed up-regulation of pro-ferroptosis genes, such as <i>Cd36,</i><i>Atm</i>, and <i>Acsl4</i>, and down-regulation of anti-ferroptosis genes, such as <i>GPX4</i>. We found that long-term abnormalities in the circadian rhythm can induce DNA damage and ferroptosis in mouse spleen. |
| first_indexed | 2024-03-09T19:01:13Z |
| format | Article |
| id | doaj.art-077a4a5a5b3c48b19ed7ffb523395c5c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:13Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-077a4a5a5b3c48b19ed7ffb523395c5c2023-11-24T05:00:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211296210.3390/ijms232112962<i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte FerroptosisRuyi He0Shijie Zhang1Jiale Yu2Xiaojie Yu3Jian Wang4Yi Qiu5Wenting Zhou6Fangyi Wang7Feng Ren8Zhiguo Liu9School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430024, ChinaDisturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in <i>Per1/Per2</i> double-knockout (DKO) and wild-type (WT) mice aged 4, 9, and 14 months. Compared to the WT mice, the DKO mice had smaller spleen white pulp (WP) and lymphocyte germinal area, as well as fewer immune cells with age—these differences were especially clear. The spleen lymphocyte mortality, malondialdehyde (MDA) levels, reactive oxygen species (ROS) levels, and ferritin-binding receptor (TFR1) levels were significantly higher in the 14-month-old DKO mice than in WT mice of the same age. Transcriptome analysis showed that most of the differentially expressed mRNAs were enriched in DNA damage repair-related pathways. In DKO mice, spleen cells showed up-regulation of pro-ferroptosis genes, such as <i>Cd36,</i><i>Atm</i>, and <i>Acsl4</i>, and down-regulation of anti-ferroptosis genes, such as <i>GPX4</i>. We found that long-term abnormalities in the circadian rhythm can induce DNA damage and ferroptosis in mouse spleen.https://www.mdpi.com/1422-0067/23/21/12962circadian clock<i>Per1/Per2</i>spleen lymphocytesferroptosis |
| spellingShingle | Ruyi He Shijie Zhang Jiale Yu Xiaojie Yu Jian Wang Yi Qiu Wenting Zhou Fangyi Wang Feng Ren Zhiguo Liu <i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis International Journal of Molecular Sciences circadian clock <i>Per1/Per2</i> spleen lymphocytes ferroptosis |
| title | <i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis |
| title_full | <i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis |
| title_fullStr | <i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis |
| title_full_unstemmed | <i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis |
| title_short | <i>Per1/Per2</i> knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis |
| title_sort | i per1 per2 i knockout affects spleen immune function in elderly mice via inducing spleen lymphocyte ferroptosis |
| topic | circadian clock <i>Per1/Per2</i> spleen lymphocytes ferroptosis |
| url | https://www.mdpi.com/1422-0067/23/21/12962 |
| work_keys_str_mv | AT ruyihe iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT shijiezhang iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT jialeyu iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT xiaojieyu iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT jianwang iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT yiqiu iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT wentingzhou iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT fangyiwang iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT fengren iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis AT zhiguoliu iper1per2iknockoutaffectsspleenimmunefunctioninelderlymiceviainducingspleenlymphocyteferroptosis |