BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis
The intestinal immune system and microbiota are emerging as important contributors to the development of metabolic syndrome, but the role of intestinal dendritic cells (DCs) in this context is incompletely understood. BATF3 is a transcription factor essential in the development of mucosal convention...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.841065/full |
| _version_ | 1818235504543399936 |
|---|---|
| author | Hussein Hamade Jasmine T. Stamps Dalton T. Stamps Shyam K. More Lisa S. Thomas Anna Y. Blackwood Nawele L. Lahcene Sofi L. Castanon Brenda C. Salumbides Yosuke Shimodaira Helen S. Goodridge Helen S. Goodridge Stephan R. Targan Kathrin S. Michelsen Kathrin S. Michelsen |
| author_facet | Hussein Hamade Jasmine T. Stamps Dalton T. Stamps Shyam K. More Lisa S. Thomas Anna Y. Blackwood Nawele L. Lahcene Sofi L. Castanon Brenda C. Salumbides Yosuke Shimodaira Helen S. Goodridge Helen S. Goodridge Stephan R. Targan Kathrin S. Michelsen Kathrin S. Michelsen |
| author_sort | Hussein Hamade |
| collection | DOAJ |
| description | The intestinal immune system and microbiota are emerging as important contributors to the development of metabolic syndrome, but the role of intestinal dendritic cells (DCs) in this context is incompletely understood. BATF3 is a transcription factor essential in the development of mucosal conventional DCs type 1 (cDC1). We show that Batf3-/- mice developed metabolic syndrome and have altered localization of tight junction proteins in intestinal epithelial cells leading to increased intestinal permeability. Treatment with the glycolysis inhibitor 2-deoxy-D-glucose reduced intestinal inflammation and restored barrier function in obese Batf3-/- mice. High-fat diet further enhanced the metabolic phenotype and susceptibility to dextran sulfate sodium colitis in Batf3-/- mice. Antibiotic treatment of Batf3-/- mice prevented metabolic syndrome and impaired intestinal barrier function. Batf3-/- mice have altered IgA-coating of fecal bacteria and displayed microbial dysbiosis marked by decreased obesity protective Akkermansia muciniphila, and Bifidobacterium. Thus, BATF3 protects against metabolic syndrome and preserves intestinal epithelial barrier by maintaining beneficial microbiota. |
| first_indexed | 2024-12-12T11:55:01Z |
| format | Article |
| id | doaj.art-fc4ade7dcad6480c90694add00f7a3e9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T11:55:01Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fc4ade7dcad6480c90694add00f7a3e92022-12-22T00:25:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.841065841065BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial HomeostasisHussein Hamade0Jasmine T. Stamps1Dalton T. Stamps2Shyam K. More3Lisa S. Thomas4Anna Y. Blackwood5Nawele L. Lahcene6Sofi L. Castanon7Brenda C. Salumbides8Yosuke Shimodaira9Helen S. Goodridge10Helen S. Goodridge11Stephan R. Targan12Kathrin S. Michelsen13Kathrin S. Michelsen14F. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesResearch Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesResearch Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United StatesThe intestinal immune system and microbiota are emerging as important contributors to the development of metabolic syndrome, but the role of intestinal dendritic cells (DCs) in this context is incompletely understood. BATF3 is a transcription factor essential in the development of mucosal conventional DCs type 1 (cDC1). We show that Batf3-/- mice developed metabolic syndrome and have altered localization of tight junction proteins in intestinal epithelial cells leading to increased intestinal permeability. Treatment with the glycolysis inhibitor 2-deoxy-D-glucose reduced intestinal inflammation and restored barrier function in obese Batf3-/- mice. High-fat diet further enhanced the metabolic phenotype and susceptibility to dextran sulfate sodium colitis in Batf3-/- mice. Antibiotic treatment of Batf3-/- mice prevented metabolic syndrome and impaired intestinal barrier function. Batf3-/- mice have altered IgA-coating of fecal bacteria and displayed microbial dysbiosis marked by decreased obesity protective Akkermansia muciniphila, and Bifidobacterium. Thus, BATF3 protects against metabolic syndrome and preserves intestinal epithelial barrier by maintaining beneficial microbiota.https://www.frontiersin.org/articles/10.3389/fimmu.2022.841065/fullMetabolic syndromeintestinal dendritic cellsintestinal permeabilitymucosal immunityBATF3colitis |
| spellingShingle | Hussein Hamade Jasmine T. Stamps Dalton T. Stamps Shyam K. More Lisa S. Thomas Anna Y. Blackwood Nawele L. Lahcene Sofi L. Castanon Brenda C. Salumbides Yosuke Shimodaira Helen S. Goodridge Helen S. Goodridge Stephan R. Targan Kathrin S. Michelsen Kathrin S. Michelsen BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis Frontiers in Immunology Metabolic syndrome intestinal dendritic cells intestinal permeability mucosal immunity BATF3 colitis |
| title | BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis |
| title_full | BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis |
| title_fullStr | BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis |
| title_full_unstemmed | BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis |
| title_short | BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis |
| title_sort | batf3 protects against metabolic syndrome and maintains intestinal epithelial homeostasis |
| topic | Metabolic syndrome intestinal dendritic cells intestinal permeability mucosal immunity BATF3 colitis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.841065/full |
| work_keys_str_mv | AT husseinhamade batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT jasminetstamps batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT daltontstamps batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT shyamkmore batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT lisasthomas batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT annayblackwood batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT nawelellahcene batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT sofilcastanon batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT brendacsalumbides batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT yosukeshimodaira batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT helensgoodridge batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT helensgoodridge batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT stephanrtargan batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT kathrinsmichelsen batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis AT kathrinsmichelsen batf3protectsagainstmetabolicsyndromeandmaintainsintestinalepithelialhomeostasis |