Oral Tolerance Induced by OVA Intake Ameliorates TNBS-Induced Colitis in Mice

Abstract

IntroductionLiterature data have shown that the consumption of dietary proteins may cause modulatory effects on the host immune system, process denominated oral tolerance by bystander suppression. It has been shown that the bystander suppression induced by dietary proteins can improve inflammatory diseases such as experimental arthritis. Here, we evaluated the effects of oral tolerance induced by ingestion of ovalbumin (OVA) on TNBS-induced colitis in mice, an experimental model for human Crohn’s disease.Methods and ResultsColitis was induced in BALB/c mice by instilling a single dose of TNBS (100 mg/kg) in ethanol into the colon. Tolerized mice received OVA (4mg/mL) dissolved in the drinking water for seven consecutive days, prior to or concomitantly with the intrarectal instillation. Control groups received protein-free water and ethanol by intrarectal route. We observed that either the prior or concomitant induction of oral tolerance were able to reduce the severity of colitis as noted by recovery of body weight gain, improvement of clinical signs and reduction of histological abnormalities. The in vitro proliferation of spleen cells from tolerant colitic mice was lower than that of control mice, the same as the frequencies of CD4+ T cells secreting IL-17 and IFN-γ. The frequencies of regulatory T cells and T cells secreting IL-10 have increased significantly in mice orally treated with OVA. The levels of inflammatory cytokines (IL-17A, TNF-α, IL-6 and IFN-γ) were lower in supernatants of cells from tolerant colitic mice, whereas IL-10 levels were higher.ConclusionOur data show that the modulation of immune response induced by oral tolerance reduces the severity of experimental colitis. Such modulation may be partially attributed to the increase of Treg cells and reduction of pro-inflammatory cytokines in peripheral lymphoid organs of tolerant mice by bystander suppression.

Adoptive transfer of CTLA4-Ig-modulated dendritic cells improves TNBS-induced colitis

“…Experimental colitis induced by TNBS instillation is characterized by chronic inflammation of the gastrointestinal tract of mice with features overlapping those seen in inflammatory bowel diseases in humans. Literature data have shown the importance of oral tolerance and treatments with tolerogenic dendritic cell for the reduction of colitis damages In this sense, previous studies of our group have shown that oral tolerance to OVA albumin as well as the adoptive transfer of dendritic cells from OVA-tolerant mice is able to reduce the damage caused by TNBS-induced colitis in syngeneic animals (23,24). We have also shown that flaxseed protein hydrolysates and phenolic fractions were able to ameliorate TNBS-induced colitis in BALB/c mice.…”

“…The results were analyzed with the FCS Express Plus Research Edition software (FCS Express Launcher). Results were expressed as proliferation index (fold change) calculated in relation to that of the control group (24,34).…”

“…Colitis induced by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in BALB/c mice, for example, generates a relatively mild inflammation of the intestinal mucosa and slight weight loss, with reestablishment of the animal within a few days after instillation. Such characteristics make this one of the experimental models most used in the study of colitis modulators(23,24).…”

Intake of Protein Hydrolysates and Phenolic Fractions Isolated from Flaxseed Ameliorates TNBS‐Induced Colitis

“…Colitis induced by TNBS mimics CD in humans, which has a predominant T helper (TH) 1 and TH17 profile . New therapies have focused on decreasing pro‐inflammatory cytokines and pathogenic TH1 and TH17 cells and on increasing the suppressive functions of T regulatory cells (Treg) to prevent the initiation and progression of the intestinal disease …”

Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice

“…The DCs that inhabit the gastrointestinal tract, however, have a proven involvement in the modulation of peripheral tolerance, through the secretion of anti-inflammatory cytokines and stimulation of Treg cells [ 22 – 25 ]. Studies from our group and others suggest that oral tolerance can generate DCs with tolerogenic profile in peripheral lymphoid organs, thus leading to the increase of regulatory T cells [ 19 , 26 ].…”