Effects Of Two Nutritional Factors On Intestinal Mucosal Immunity And The Development Of The Immune System

Appropriate nutritional level is an important guarantee for the normal physiological function and continuous development of the children's immune system. The nutritional intervention for children in reality has two major cases:to correct the impaired function and blocked development of the immune-system caused by nutrient unbalance, rehabilitating the body's defensive quality to diseases; through constructing a good nutritional environment, promote the development of the immune system and enhance the immunity in childhood, thereby preventing diseases and promoting long-term health. In this paper, we discussed the mechanism of vitamin A modulation of the intestinal mucosal immunity, as well as the role of bifidobacteria on the development of both the gut and systemic immunity, to enrich the knowledge about the relationship between children's nutrition and immunity in these two aspects.Objectives In order to clarify the mechanism of vitamin A (VA) modulation of intestinal mucosal immunity, we investigated the effects and approaches of retinoic acid (RA), an active metabolite of VA, on the number, maturation and cytokine production of intestinal dendritic cells (DCs), to probe into its role at the initial step of immune response.Methods Peyer's patches (PPs) from the healthy adult SD rats were cultured in vitro, with all-trans retinoic acid (at-RA) or/and Ro 41-5253 (RO), a specific antagonist for retinoic acid receptor a were added into the culture. The tissues were harvested 24 h and 48 h later for the following analysis.1. Surface marker expressions on DCs were assessed using direct immunofluorescent antibodies and flow cytometer to evaluate the effect of RA on the number (the percentage of OX-62 positive cells) and maturation (fluorescence intensity of OX6 and CD86) of DCs in cultured PPs.2. By using RT-quantitative PCR, the effect of RA on the gene expression of cytokines and RARa in PPs were examined. Results 1. After culture for both 24 h and 48 h, the number of DCs in PPs showed no significant difference among the RA, RA+RO, and control group, but treated with at-RA promoted the maturation of DCs, with the effect most notable at 24 h of culture; 2. at-RA treatment led to reduced IL-12 (mainly secreted by DCs) and IFN-γ(Thl cytokine) but increased IL-10 (regulatory cytokine) gene expression in PPs, whereas there was no significant difference in IL-4 (Th2 cytokine) mRNA compared with the control. Moreover, RARa gene expression in PPs was up-regulated by at-RA; 3. All the actions of at-RA described above were reversed when cultured along with Ro 41-5253.Conclusion 1.Retinoic acid could promote the maturation of DCs in cultured PPs, and make immune response bias to regulatory T cell, thus be potent in maintaining homeostasis of the gut immunity, and preventing the emergence of a harmful inflammatory state; 2. RARa plays a very important role in the regulation of mucosal immunity by retinoic acid.Objectives We established an animal model, the rat with intestinal bifidobacteria minimisation or extra colonization, to explore how intestinal bifidobacteria affect the development of both the gut and systemic immunity in early life, especially its modulation on the differentiation, maturation and function of DCs, the type of T-cell responses and immunoglobulin synthesis, providing theoretical and experimental basis for the proper usage of probiotics in children in reality.Methods Neonatal SD rats housed under strict barrier systems were fed from birth with sufficient antibiotics (bifidobacteria minimisation group) or supplemented daily with live Bifidobacterium longum (bifidobacteria supplementation group). The role of intestinal bifidobacteria on the following immune-development indices was determined at one, three and six weeks old respectively:1. By use of flow cytometry, the number (the percentage of OX-62 positive cells) and maturation (fluorescence intensity of CD86) of DCs, the proportion of each T-cell subset in PPs, spleen and peripheral blood were detected, as well as the development of T cells in thymus.2. The mRNA levels of cytokines in intestinal mucosa and cultured peripheral blood mononuclear cells (PBMCs) were measured by RT-PCR, and production of these cytokines in plasma was determined by ELISA.3. The secretion of IgG and IgM by PBMCs were detected by ELISA.Results 1. Minimisation of the intestinal bifidobacteria delayed maturation of DCs in PPs, whereas supplementation with bifidobacteria promoted DC maturation in PPs. Besides, in bifidobacteria minimisation group, the differentiation of immature CD4+CD8+T cell to mature CD4+or CD8+T cell was delayed in thymus; 2. Bifidobacteria minimisation down-regulated IL-12, IL-10 mRNA and the IFN-y/IL-4 (Thl/Th2) mRNA ratio in intestinal mucosa, increased IL-4 secretion in the plasma, decreased IFN-y mRNA in cultured PBMCs; bifidobacteria supplementation up-regulated IL-12, IFN-y, IL-10 mRNA and the IFN-y/IL-4 ratio in intestinal mucosa, increased IFN-y gene expression in PBMCs; 3. Bifidobacteria minimisation group had a decreased production of IgM by cultured PBMCs, whereas bifidobacteria supplementation group had an increased secretion of it.Conclusion In early life, intestinal bifidobacteria colonisation could:1. promote DC maturation and its espression of IL-12 in PPs; 2. influence the development of T cells in thymus; 3. favour the T-helper cell response of the body in a Thl type and meanwhile ensure the development of regulatory T cell response in the gut; 4. enhance antibody synthesis by PBMCs, thereby having a potential role in strengthening the humoral immunity.