Sección de Estudios de Postgrado e Investigación, Laboratorio de Inmunidad de Mucosas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luís y Díaz Mirón, México, D.F., Mexico.
Immunol Lett. 2010 Jan 18;128(1):59-67. doi: 10.1016/j.imlet.2009.11.005. Epub 2009 Nov 17.
Few reports exist on the differences in cell populations or immunological functions between the proximal and distal segments of the small intestine (SI). In the current contribution we analyzed the expression of the polymeric immunoglobulin receptor (pIgR) and alpha chains as well as the density of IgA-producing cells from the proximal and distal intestinal segments from Balb/c mice. Furthermore, by using real-time RT-PCR we quantified the expression of cytokines (TNF-alpha, IFN-gamma, IL-4 and TGF-beta), Toll-like receptor-4 (TLR-4), and the glucocorticoid receptor (GR) involved in pIgR expression in intestinal epithelial cells (IEC). In this study, for the first time it has been demonstrated that the expression of the pIgR as well as alpha chain was greater in the proximal than the distal segment of the small intestine of normal mice. Moreover, we found striking differences in the expression of cytokines at the different intestinal compartments. Whereas the expression of TNF-alpha, IFN-gamma and TGF-beta was higher in lamina propria lymphocytes (LPL) of the distal than proximal segment, it was higher in IEC of the proximal than distal segment. In contrast, the expression of the gene for IL-4 was higher in the LPL of the proximal segment and the IEC of the distal segment. Although the overall expression of TNF-alpha, IL-4, IFN-gamma and TGF-beta was higher in the whole mucosa of the distal than proximal segment, we propose that cytokines produced by epithelial cells (TNF-alpha, IFN-gamma and TGF-beta) autocrinally up-regulate the expression of mRNA for the pIgR. Finally the expression of the GR was higher in the proximal segment, while the expression of the gene for TLR-4 was significantly higher in the IEC of the distal than proximal segment. The higher expression of pIgR found in the proximal segment is probably related to the effect on epithelial cells of the higher production of TNF-alpha, IFN-gamma and TGF-beta, as well as the higher expression of the glucocorticoid receptors. The increased expression of pIgR in the proximal segment appears primarily responsible for the increased secretory IgA levels in the small intestine of mice. These results confirm and extend previous findings supporting the compartmentalization of the intestinal immune system.
关于小肠（SI）近端和远端段之间的细胞群体或免疫功能的差异，目前仅有少量报道。在本研究中，我们分析了 Balb/c 小鼠近端和远端肠道段多聚合免疫球蛋白受体（pIgR）和α链的表达以及 IgA 产生细胞的密度。此外，我们还通过实时 RT-PCR 定量分析了参与肠上皮细胞（IEC）中 pIgR 表达的细胞因子（TNF-α、IFN-γ、IL-4 和 TGF-β）、Toll 样受体-4（TLR-4）和糖皮质激素受体（GR）的表达。在这项研究中，我们首次证明了 pIgR 及其α链的表达在正常小鼠的小肠近端段比远端段更为显著。此外，我们发现不同肠段细胞因子的表达存在显著差异。尽管 TNF-α、IFN-γ 和 TGF-β在远端段的固有层淋巴细胞（LPL）中的表达高于近端段，但在近端段的 IEC 中的表达高于远端段。相反，IL-4 的基因在近端段的 LPL 和远端段的 IEC 中的表达更高。尽管 TNF-α、IL-4、IFN-γ 和 TGF-β 的整体表达在远端段的整个黏膜中高于近端段，但我们提出，上皮细胞产生的细胞因子（TNF-α、IFN-γ 和 TGF-β）自身上调 pIgR 的 mRNA 表达。最后，GR 的表达在近端段更高，而 TLR-4 的基因表达在远端段的 IEC 中明显高于近端段。近端段 pIgR 的高表达可能与 TNF-α、IFN-γ 和 TGF-β产生的更高水平有关，以及糖皮质激素受体的更高表达有关。近端段 pIgR 的表达增加似乎主要负责增加小鼠小肠中分泌型 IgA 的水平。这些结果证实并扩展了先前支持肠道免疫系统分区化的发现。
