BACTERIAL;EPITHELIAL; T-CELL INTERACTIONS IN GUT MUCOSA

在无菌小鼠的肠道中，淋巴组织的浸润度很低。在殖民后与 正常菌群：淋巴细胞大量涌入和激活肠粘膜， 受控或生理性炎症的现象已经确立。它一般都是 认识到调节细胞在维持这种状态中起着关键作用。三人组 细菌上皮细胞之间的相互作用：T细胞在各种不同的 学习。我们认为细菌与上皮细胞的相互作用促进了一种环境， 可以生成特定的树。共生菌群可上调/诱导 非经典I类分子参与Tregs的激活并促进选择性 趋化因子的产生，将Treg或Treg前体招募到粘膜和上皮中。 在上皮内，晶状体上皮细胞上的非经典I类分子呈递的细菌抗原可以 激活树起作用：维持正常的生理功能 炎症状态。 在炎症性肠病中，这一过程中的任何数量的缺陷都可能导致 监管。我们已经证明IBD LEC显示gplSO和gplSO表达缺陷 CDld.这些缺陷背后的机制(S)尚未确定。更改中 趋化因子或细胞因子的产生可能解释了这些观察结果。这项提议将检验 这一模式的不同方面(在健康和疾病方面--都在人体组织中)。 具体目标#1.确定正常和IBD患者中存在(或不存在)哪些Treg 并将其与IBD非经典I类分子表达缺陷相关联 (目标2)。IBD组织中tre细胞的缺陷是选择性的还是全局性的 特雷格斯？ 特定目标2：确定非经典I类分子的表达和调节 并确定IBD LECs在表达上的缺陷。

In a germ free mouse there is minimal lymphoid infiltration in the gut. Upon colonization with normal flora there is significant influx and activation of lymphocytes into the gut mucosa and the phenomenon of controlled or physiologic inflammation is established. It is generally recognized that regulatory cells play a key role in the maintenance of this state. A trialogue between bacterial epithelial: T cell interactions has been demonstrated in a variety of different studies. We propose that bacterial:epithelial interactions promote an environment where specific Tregs can be generated. Commensal flora may upregulate/induce the expression of nonclassical class I molecules invovled in the activation of Tregs as well as promote selective chemokine production that recruits Tregs or Treg precursors into the mucosa and epithelium. Within the epithelium bacterial Ags presented by nonclassical class I molecules on lECs can activate Tregs to effect their function: the maintenance of the normal physiologic inflammatory state. In inflammatory bowel disease any number of defects in this process can lead to a failure in regulation. We have already shown that IBD lECs display defective expression of gplSO and CDld. The mechanism(s) underlying these defects have not been defined. Alteration in chemokine or cytokine production may account for these observations. This proposal will test distinct aspects of this model (in health and disease - all in human tissues). Specific Aim #1. Determine which Tregs are present (or absent) in the normal and IBD intestine and correlate these with defects in non-classical class I molecule expression in IBD (aim #2). Is the defect in TrE cells in IBD tissues reflective of a selective or global defect in Tregs? Specific Aim #2: Determine the expression and regulation of non-classical class I molecules on intestinal epithelial cells and define defects in expression on IBD lECs.