RT Journal Article
SR Electronic
T1 Obesity Modulates Intestinal Intraepithelial T Cell Persistence, CD103 and CCR9 Expression, and Outcome in Dextran Sulfate Sodium–Induced Colitis
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 3427
OP 3435
DO 10.4049/jimmunol.1900082
VO 203
IS 12
A1 Park, Christa
A1 Cheung, Kitty P.
A1 Limon, Natalie
A1 Costanzo, Anne
A1 Barba, Cindy
A1 Miranda, Nadia
A1 Gargas, Shannon
A1 Johnson, Andrew M. F.
A1 Olefsky, Jerrold M.
A1 Jameson, Julie M.
YR 2019
UL http://www.jimmunol.org/content/203/12/3427.abstract
AB Diet-induced obese mice exhibit reduced αβ and γδ IEL persistence within 7 wk.Obese mice are more susceptible to dextran sulfate sodium–induced colitis.Diet-induced weight loss restores IEL number and improves outcome in colitis.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.