| First Author | Park C | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 12 | Pages | 3427-3435 |
| PubMed ID | 31712385 | Mgi Jnum | J:282212 |
| Mgi Id | MGI:6379912 | Doi | 10.4049/jimmunol.1900082 |
| Citation | Park C, et al. (2019) Obesity Modulates Intestinal Intraepithelial T Cell Persistence, CD103 and CCR9 Expression, and Outcome in Dextran Sulfate Sodium-Induced Colitis. J Immunol 203(12):3427-3435 |
| abstractText | 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 alphabeta and gammadelta 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 alphabeta and gammadelta IEL persistence as obesity progresses with a different mechanism in alphabeta versus gammadelta IEL populations. CD4(+) and CD4(+)CD8(+) alphabeta intraepithelial T lymphocytes exhibit reduced homeostatic proliferation in obesity, whereas both alphabeta and gammadelta 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-alpha. 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. |
