Neonatal mucosal immune stimulation by microbial superantigen improves the tolerogenic capacity of CD103(+) dendritic cells.
Neonatal mucosal immune stimulation by microbial superantigen improves the tolerogenic capacity of CD103(+) dendritic cells.
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DOI：
10.1371/journal.pone.0075594
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Östman S
中科院分区：
文献类型：
--
作者：
Stern A;Wold AE;Östman S
食物过敏代表未能对膳食蛋白质产生耐受性。随着婴儿期接触微生物的减少，食物过敏的患病率也随之增加。在小鼠中，新生儿经口暴露于强烈 T 细胞刺激的超抗原葡萄球菌肠毒素 A (SEA)，增强了对成年生活中遇到的新抗原产生口服耐受的能力。肠道中的抗原呈递细胞 CD103+ 树突状细胞 (DC) 被认为参与口服耐受的发展，因为它们将幼稚 T 细胞转化为 FoxP3+ 调节性 T 细胞 (Treg)。该功能取决于它们将维生素 A 转化为视黄酸的能力，由视黄醛脱氢酶 (RALDH) 进行。在这里，新生小鼠接受了超抗原和 DC 功能治疗，并在六周龄时检查了耐受能力。我们观察到，在新生儿喂养超抗原的小鼠中，CD11c+ DC 的 RALDH 表达增加，并且在体外更有效地诱导表达 Foxp3 表达以刺激 T 细胞。此外，这些小鼠在小肠固有层中显示出 FoxP3+ T 细胞的积累，并且在体内口服耐受诱导后具有更多 Ag 特异性的 FoxP3+ T 细胞。此外，如果维生素A代谢受到抑制，口服耐受性的改善（通过增强对食物过敏的保护来证明）就会被消除。这些观察结果有助于了解新生儿期强烈的免疫刺激如何影响免疫系统的成熟，并表明这种刺激可能会降低以后发生过敏的风险。
Food allergy represents failure to develop tolerance to dietary proteins. Food allergy has increased in prevalence in parallel with decreased exposure to microbes during infancy. In mice, neonatal peroral exposure to the strongly T cell stimulating superantigen staphylococcal enterotoxin A (SEA), enhances the capacity to develop oral tolerance to a novel antigen encountered in adult life. A population of antigen-presenting cells in the gut, the CD103+ dendritic cells (DCs), is thought to be involved in oral tolerance development, as they convert naïve T cells into FoxP3+ regulatory T cells (Treg). This function depends on their capacity to convert vitamin A to retinoic acid, carried out by the retinal aldehyde dehydrogenase (RALDH) enzyme. Here, newborn mice were treated with superantigen and DC function and tolerogenic capacity was examined at six weeks of age. We observed that, in mice fed superantigen neonatally, the CD11c+ DCs had increased expression of RALDH and in vitro more efficiently induced expression Foxp3 expression to stimulated T cells. Further, these mice showed an accumulation of FoxP3+ T cells in the small intestinal lamina propria and had a more Ag-specific FoxP3+ T cells after oral tolerance induction in vivo. Moreover, the improved oral tolerance, as shown by increased protection from food allergy, was eradicated if the Vitamin A metabolism was inhibited. These observations contribute to the understanding of how a strong immune stimulation during the neonatal period influences the maturation of the immune system and suggests that such stimulation may reduce the risk of later allergy development.
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DOI：
10.1126/science.1202947
发表时间：
2011-04-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Qureshi OS;Zheng Y;Nakamura K;Attridge K;Manzotti C;Schmidt EM;Baker J;Jeffery LE;Kaur S;Briggs Z;Hou TZ;Futter CE;Anderson G;Walker LS;Sansom DM
通讯作者：
Sansom DM
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.1196/annals.1309.002
发表时间：
2004-01-01
期刊：
ORAL TOLERANCE: NEW INSIGHTS AND PROSPECTS FOR CLINICAL APPLICATION
影响因子：
--
作者：
Garside, P;Millington, O;Smith, KM
通讯作者：
Smith, KM
影响因子：
4.4
作者：
Misra, N;Bayry, J;Kaveri, SV
通讯作者：
Kaveri, SV
影响因子：
6.1
作者：
Lundell, A-C.;Adlerberth, I.;Rudin, A.
通讯作者：
Rudin, A.