Immunomodulation of experimental colitis via caloric restriction: role of Nk1.1+ T cells.
Inflammatory bowel diseases are immune-mediated disorders. Dietary restriction and NK1.1+ liver-associated lymphocytes (LAL) are considered to be involved in immunomodulation of autoimmune diseases. Our aim was to evaluate the effect of caloric restriction on experimental colitis and to determine NK1.1+ LAL function in immunoregulation. Experimental colitis was induced in C57 black mice by intracolonic instillation of trinitrobenzene sulfonic acid. Caloric restriction to 60% of the daily requirement was started 2 weeks prior to, or simultaneously with, colitis induction and continued throughout the study. Control mice were fed ad libitum. Colitis was assessed by standard clinical and macroscopic scores. To determine the mechanism involved in immunomodulation, liver lymphocytes were isolated and analyzed for NK1.1+ T-cell markers by FACS. T-cell function was evaluated by T-cell proliferation. Serum cytokines were measured by ELISA. Dietary restriction to 60% markedly ameliorated experimental colitis in both groups. These mice gained weight and showed improved macroscopic parameters of colitis. NK1.1+ LAL numbers increased fourfold and NKT cytotoxicity twofold in caloric-restricted mice. The antigen-specific T-cell proliferation index decreased (from 4.45 in controls to 1.15), and IFN-gamma and IL-12 serum levels decreased (from 290 to 200 pg and from 122 to 53 pg, respectively) in caloric-restricted mice. Our conclusion was that dietary restriction induced immunomodulation of experimental colitis and ameliorated the disease. This effect was mediated via an increase in NK1.1+ T lymphocytes, which may play a critical role in keeping the T-cell balance in immunoregulation.
Shibolet
Oren
O
Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. Shibolet@hadassah.org.il
Alper
Roslana
R
Avraham
Yosefa
Y
Berry
Elliot M
EM
Ilan
Yaron
Y
D000818:Animals; D016516:CD4-CD8 Ratio; D031204:Caloric Restriction; D002455:Cell Division / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid; D014407:Tumor Cells, Cultured
D016207:Cytokines; D014302:Trinitrobenzenesulfonic Acid