IL-22 produced by innate lymphoid cells (ILCs) and CD4+ T cells plays an important role in host defense and mucosal homeostasis, thus it is important to investigate the mechanisms that regulate IL-22 production. We investigated the regulation IL-22 production by CD4+ T cells. Here we show that IL-21 triggers IL-22, but not IL-17 production by CD4+ T cells. STAT3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). Moreover, IL-21 and AhR signaling in T cells control IL-22 production and the development of dextran sodium sulfate-induced colitis in ILC-deficient mice. Thus, we have identified IL-21 as an inducer of IL-22 production in CD4+ T cells in vitro and in vivo.

Objective The effects of high‐refined carbohydrate‐containing diet (HC) on inflammatory parameters and metabolic disarrangement of adipose tissue are poorly understood. The aim of this study was to evaluate the timing and progression of metabolic and inflammatory dysfunction induced by HC diet in mice. Design and Methods BALB/c mice were fed chow or HC diet for 1 and 3 days, 1, 2, 4, 6, 8, 10, and 12 weeks. Results Animals given HC diet exhibited acute and sustained increase in visceral adiposity, glucose intolerance, low insulin sensitivity, hyperlipemia, acute increase in mRNA expression of ACC, LPL, PPARγ, SREBP‐1, and ChREBP and altered circulating levels of adiponectin, resistin, and leptin. There was leucocyte rolling and adhesion on adipose tissue microvessels already at 3 days and until 8 weeks of HC diet. Adipose tissue of mice had increased number of macrophages (M1 and M2), lymphocytes (CD8+ and CD4+Foxp3+), and neutrophils (GR1+) already at 3 days after initiation of HC diet. Overall, concentration of cytokines and chemokines, TNF‐α, IL‐6, IL‐10, TGF‐β1, CCL2, and CXCL1, in adipose tissue was elevated throughout the experimental period. Levels of IL‐10 and TGF‐β1 tended to reach baseline levels at 12 weeks of HC diet. Conclusions We describe a novel murine model of fat pad expansion induced by HC diet that is characterized by early onset and sustained adipose tissue inflammation and metabolic disarrangement. The acute inflammatory response in adipose tissue occurs very early and is sustained, suggesting that adipose tissue inflammation is a homeostatic mechanism to regulate nutrient overload and adipose expansion.

Tributyrin (TBT) is a TAG composed of three butyric acids that has beneficial effects on ulcerative colitis due to its trophic, anti-inflammatory, pro-apoptotic and anti-carcinogenic properties. The goal of the present study was to evaluate the efficacy and mechanisms of action of TBT supplementation in the prevention of mucosal damage in experimental colitis. Mice received either a control diet or a TBT-supplemented diet for 15 d. Colitis was induced by dextran sodium sulphate administration during the last 7 d. Mucosal damage and the activation of immune cells and cytokines were determined by histological score, flow cytometry and ELISA. Leucocyte rolling and adhesion were assessed by intravital microscopy. Oxidative stress was determined by monitoring hydroperoxide concentration and evaluating superoxide dismutase (SOD) and catalase activities. Intestinal permeability was analysed using diethylenetriaminepentaacetate acid ( 99mTc DTPA). Compared with the colitis group, the animals in the colitis þ TBT group had reduced mucosal damage and neutrophil and eosinophil mucosal infiltration, which were associated with a higher percentage of regulatory T cells (Treg) and higher levels of transforming growth factor b and IL-10 in the lamina propria. The level of in vivo leucocyte adhesion in the colon microvasculature was reduced after TBT supplementation. A lower level of hydroperoxide and higher levels of SOD and catalase activities were associated with TBT supplementation. TBT-supplemented mice showed reduced intestinal permeability to the levels intermediate between the control and colitis groups. In conclusion, the present results show that TBT has positive effects on colonic restructuring in experimental colitis. Additionally, TBT supplementation changes the immune response by controlling inflammation and regulating the expression of anti-inflammatory cytokines and Treg.

Aging is reported to be associated with decline in oral tolerance induction, which is initiated at the intestinal mucosal surface. Herein, we examined the effect of aging in T cells and cytokines at the intestinal mucosa that might be involved in oral tolerance induction. Frequencies of regulatory-type IEL subsets such as TCRγδ+ and TCRαβ+CD8αα+ were lower in aged mice. Mucosal CD4+CD25+Foxp3+ and CD4+LAP+ T cells increased with aging but activated CD44+CD4+ mucosal T cells also augmented. Production of TGF-β and IL-10 in the small intestine of old mice was reduced. Moreover, the ability of mucosal dendritic cells of aged mice to stimulate TGF-β secretion and differentiation of CD4+LAP+ T cells in co-culture studies also declined with aging. Reduction in these regulatory-type cytokines and T cells may help to explain the decline in susceptibility to oral induction during aging. However, not all mucosal regulatory elements were altered by aging and CD4+CD25+Foxp3+ T cells were especially resistant to changes. Persistence of some mechanisms of regulation might play a critical role in maintaining mucosal homeostasis during aging.

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Therefore, HSB represents a novel model of obesity-inducing diet that was efficient in triggering alterations compatible with metabolic syndrome as well as impairment in immune regulatory parameters.

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