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

Abstract

IntroductionIn addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms.Methods and resultsTo induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN-γ were lower in supernatants of cells from mice treated with nDCs.ConclusionThe results allow us to conclude that the adoptive transfer of cells expressing CD11c is able to reduce the clinical and immunological signs of drug-induced colitis. Adoptive transfer of CD11c+DC isolated from both naive and tolerant mice altered the proliferative and T cell responses. To the best of our knowledge, there is no previously published data showing the protective effects of DCs from naïve or tolerant mice in the treatment of colitis.

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.…”

“…Thickening of the colon wall was measured in micrometers using the Infinity Analyze Nikon H600L (100X). The final scores represent the mean ± S.E.M (23,34).…”

“…Controls were performed with irrelevant isotype staining. Acquisitions were performed with FACScalibur flow cytometer and analyzes were done with the FCS Express 5 Plus, Research Edition software (23,34)…”

“…Fluorescence were acquired in FACSCalibur cytometer and analyzed with FCAP Array TM Software Version 3.0 (BD). IL-9 determination was assayed with CBA flex set (BD Cytometric Flex Set Th9, San Diego, USA) (23,34)…”

“…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).…”