Obesity Modulates Intestinal Intraepithelial T Cell Persistence, CD103 and CCR9 Expression, and Outcome in Dextran Sulfate Sodium–Induced Colitis
| Autor: | Andrew M.F. Johnson, Shannon Gargas, Jerrold M. Olefsky, Julie M. Jameson, Christa Park, Kitty P. Cheung, Cindy Barba, Nadia Delgadillo Miranda, Anne Costanzo, Natalie Limon |
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| Rok vydání: | 2019 |
| Předmět: |
Male
T cell Immunology Population Fluorescent Antibody Technique CCR9 Inflammation Thymus Gland Biology Diet High-Fat Severity of Illness Index Receptors Tumor Necrosis Factor Immunomodulation Mice Receptors CCR 03 medical and health sciences 0302 clinical medicine Antigens CD medicine Animals Immunology and Allergy Obesity Colitis education Intraepithelial Lymphocytes education.field_of_study Dextran Sulfate Age Factors medicine.disease Immunohistochemistry Intestinal epithelium Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Intraepithelial lymphocyte medicine.symptom Integrin alpha Chains Biomarkers Spleen CD8 Signal Transduction 030215 immunology |
| Zdroj: | The Journal of Immunology. 203:3427-3435 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Obesity impacts over 30% of the United States population, resulting in a wide array of complications. Included among these is the deterioration of the intestinal barrier, which has been implicated in type 2 diabetes and susceptibility to bacterial transepithelial migration. The intestinal epithelium is maintained by αβ and γδ intraepithelial T lymphocytes, which migrate along the epithelia, support epithelial homeostasis, and protect from infection. In this study, we investigate how obesity impacts intraepithelial lymphocyte (IEL) persistence and function in intestinal homeostasis and repair. Mice were fed a high-fat diet to induce obesity and to study immunomodulation in the intestine. There is a striking reduction in αβ and γδ IEL persistence as obesity progresses with a different mechanism in αβ versus γδ IEL populations. CD4+ and CD4+CD8+ αβ intraepithelial T lymphocytes exhibit reduced homeostatic proliferation in obesity, whereas both αβ and γδ IELs downregulate CD103 and CCR9. The reduction in intraepithelial T lymphocytes occurs within 7 wk of high-fat diet administration and is not dependent on chronic inflammation via TNF-α. Young mice administered a high-fat diet upon weaning exhibit the most dramatic phenotype, showing that childhood obesity has consequences on intestinal IEL seeding. Together, this dysfunction in the intestinal epithelium renders obese mice more susceptible to dextran sulfate sodium–induced colitis. Diet-induced weight loss restores IEL number and CD103/CCR9 expression and improves outcome in colitis. Together, these data confirm that obesity has immunomodulatory consequences in intestinal tissues that can be improved with weight loss. |
| Databáze: | OpenAIRE |
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