Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice
Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. However, the mechanisms that trigger the underlying adipose tissues inflammation are not completely understood. Here, we show that the E3 ubiquitin ligase March1 controls the phenotypic and functional prope...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01953/full |
| _version_ | 1818319426509864960 |
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| author | Abdelilah Majdoubi Jun Seong Lee Osama A. Kishta Mohammad Balood Mohamed Abdelwafi Moulefera Satoshi Ishido Sébastien Talbot Cheolho Cheong Thierry Alquier Jacques Thibodeau |
| author_facet | Abdelilah Majdoubi Jun Seong Lee Osama A. Kishta Mohammad Balood Mohamed Abdelwafi Moulefera Satoshi Ishido Sébastien Talbot Cheolho Cheong Thierry Alquier Jacques Thibodeau |
| author_sort | Abdelilah Majdoubi |
| collection | DOAJ |
| description | Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. However, the mechanisms that trigger the underlying adipose tissues inflammation are not completely understood. Here, we show that the E3 ubiquitin ligase March1 controls the phenotypic and functional properties of CD8+ T cells in mice white adipose tissue. In a diet-induced obesity model, mice lacking March1 [March1 knockout (KO)] show increased insulin resistance compared to their WT counterparts. Also, in obese March1 KO mice, the proportions of effector/memory (Tem) and resident/memory (Trm) CD8+ T cells were higher in the visceral adipose tissue, but not in the spleen. The effect of March1 on insulin resistance and on the phenotype of adipose tissue CD8+ T cells was independent of major histocompatibility complex class II ubiquitination. Interestingly, we adoptively transferred either WT or March1 KO splenic CD8+ T cells into obese WT chimeras that had been reconstituted with Rag1-deficient bone marrow. We observed an enrichment of Tem and Trm cells and exacerbated insulin resistance in mice that received March1 KO CD8 T cells. Mechanistically, we found that March1 deficiency alters the metabolic activity of CD8+ T cells. Our results provide additional evidence of the involvement of CD8+ T cells in adipose tissue inflammation and suggest that March1 controls the metabolic reprogramming of these cells. |
| first_indexed | 2024-12-13T10:08:56Z |
| format | Article |
| id | doaj.art-05ca7d4f09584924be320d026703f95e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T10:08:56Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-05ca7d4f09584924be320d026703f95e2022-12-21T23:51:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01953551106Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese MiceAbdelilah Majdoubi0Jun Seong Lee1Osama A. Kishta2Mohammad Balood3Mohamed Abdelwafi Moulefera4Satoshi Ishido5Sébastien Talbot6Cheolho Cheong7Thierry Alquier8Jacques Thibodeau9Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, CanadaDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, CanadaDepartment of Microbiology, Hyogo College of Medicine, Nishinomiya, JapanDépartement de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, CanadaInstitut de Recherches Cliniques de Montréal (IRCM), Montreal, QC, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal Diabetes Research Center, and Département de Médicine, Université de Montréal, Montreal, QC, CanadaDépartement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, CanadaObesity is a major risk factor for the development of insulin resistance and type 2 diabetes. However, the mechanisms that trigger the underlying adipose tissues inflammation are not completely understood. Here, we show that the E3 ubiquitin ligase March1 controls the phenotypic and functional properties of CD8+ T cells in mice white adipose tissue. In a diet-induced obesity model, mice lacking March1 [March1 knockout (KO)] show increased insulin resistance compared to their WT counterparts. Also, in obese March1 KO mice, the proportions of effector/memory (Tem) and resident/memory (Trm) CD8+ T cells were higher in the visceral adipose tissue, but not in the spleen. The effect of March1 on insulin resistance and on the phenotype of adipose tissue CD8+ T cells was independent of major histocompatibility complex class II ubiquitination. Interestingly, we adoptively transferred either WT or March1 KO splenic CD8+ T cells into obese WT chimeras that had been reconstituted with Rag1-deficient bone marrow. We observed an enrichment of Tem and Trm cells and exacerbated insulin resistance in mice that received March1 KO CD8 T cells. Mechanistically, we found that March1 deficiency alters the metabolic activity of CD8+ T cells. Our results provide additional evidence of the involvement of CD8+ T cells in adipose tissue inflammation and suggest that March1 controls the metabolic reprogramming of these cells.https://www.frontiersin.org/article/10.3389/fimmu.2020.01953/fullMarch1obesityT cell metabolismmemory CD8 T cell |
| spellingShingle | Abdelilah Majdoubi Jun Seong Lee Osama A. Kishta Mohammad Balood Mohamed Abdelwafi Moulefera Satoshi Ishido Sébastien Talbot Cheolho Cheong Thierry Alquier Jacques Thibodeau Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice Frontiers in Immunology March1 obesity T cell metabolism memory CD8 T cell |
| title | Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice |
| title_full | Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice |
| title_fullStr | Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice |
| title_full_unstemmed | Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice |
| title_short | Lack of the E3 Ubiquitin Ligase March1 Affects CD8 T Cell Fate and Exacerbates Insulin Resistance in Obese Mice |
| title_sort | lack of the e3 ubiquitin ligase march1 affects cd8 t cell fate and exacerbates insulin resistance in obese mice |
| topic | March1 obesity T cell metabolism memory CD8 T cell |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01953/full |
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