Hundorfean Gheorghe, Zimmer Klaus-Peter, Strobel Stephan, Gebert Andreas, Ludwig Diether, Büning Jürgen
Dept. of Internal Medicine I, Univ. Hospital of Schleswig-Holstein, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G798-808. doi: 10.1152/ajpgi.00135.2007. Epub 2007 Aug 2.
In contrast to healthy conditions, intestinal epithelial cells (IECs) stimulate proinflammatory CD4+ and CD8+ T cells during Crohn's disease (CD). The underlying regulatory mechanisms remain unknown. Here we investigated the epithelial expression of major histocompatibility complex (MHC) I and MHC II and its interference with endocytic pathways, in vivo. During ileoscopy, ovalbumin (OVA) was sprayed onto ileal mucosa of CD patients (ileitis and remission) and controls. The epithelial traffic of OVA and MHC I/II pathways were studied in biopsies using fluorescence and electron microscopy. We found MHC I and MHC II to accumulate within multivesicular late endosomes (MVLE) of IECs. Faint labeling for these molecules was seen in early endosomes and lysosomes. MVLE were entered by OVA 10 min after exposure. Exosomes carrying MHC I, MHC II, and OVA were detected in intercellular spaces of the epithelium. OVA trafficking and labeling patterns for MHC I and MHC II in IECs showed no differences between CD patients and controls. Independent of inflammatory stimuli, MHC I and MHC II pathways intersect MVLE in IECs, which were efficiently targeted by luminal antigens. Similar to MHC II-enriched compartments in professional antigen presenting cells, these MVLE might be critically involved in MHC I- and MHC II-related antigen processing in IECs and the source of epithelial-released exosomes. The access of luminal antigens to MHC I in MVLE might indicate that the presentation of exogenous antigens by IECs must not be restricted to MHC II but might also occur as "cross-presentation" via MHC I to CD8+ T cells.
与健康状况相反，在克罗恩病（CD）期间，肠道上皮细胞（IEC）会刺激促炎性CD4+和CD8+ T细胞。其潜在的调控机制仍不清楚。在此，我们在体内研究了主要组织相容性复合体（MHC）I和MHC II的上皮表达及其对胞吞途径的干扰。在回肠镜检查期间，将卵清蛋白（OVA）喷洒到CD患者（回肠炎和缓解期）及对照组的回肠黏膜上。使用荧光和电子显微镜在活检组织中研究OVA的上皮转运以及MHC I/II途径。我们发现MHC I和MHC II在IEC的多囊泡晚期内体（MVLE）中积累。在早期内体和溶酶体中可见这些分子的微弱标记。暴露10分钟后，OVA进入MVLE。在上皮细胞间空间中检测到携带MHC I、MHC II和OVA的外泌体。IEC中OVA的转运以及MHC I和MHC II的标记模式在CD患者和对照组之间没有差异。独立于炎症刺激，MHC I和MHC II途径在IEC中与MVLE相交，而MVLE被腔内抗原有效靶向。类似于专业抗原呈递细胞中富含MHC II的区室，这些MVLE可能在IEC中与MHC I和MHC II相关的抗原加工以及上皮释放的外泌体来源中起关键作用。腔内抗原进入MVLE中的MHC I可能表明IEC对外源抗原的呈递不一定局限于MHC II，也可能通过MHC I以“交叉呈递”的方式发生至CD8+ T细胞。
