Laboratorio de Investigación en el Sistema Inmune - LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
PLoS One. 2013 Sep 13;8(9):e73658. doi: 10.1371/journal.pone.0073658. eCollection 2013.
The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B(+) T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B(+) B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.
MICA/B 基因（主要组织相容性复合体 I 链相关基因 A 和 B）编码非传统的 I 类 HLA 分子，它们在抗原呈递中没有作用。MICA/B 可被多种应激条件上调，如热休克、氧化应激、肿瘤转化和病毒感染。特别是，MICA/B 在肠上皮细胞中表达，当它们被上皮内淋巴细胞上存在的激活型 NKG2D 受体识别时，可介导肠上皮细胞凋亡。这一机制被认为在活动性乳糜泻（CD）中起主要致病作用。鉴于 MICA/B 在 CD 发病机制中的重要性，我们研究了它们在 CD 患者十二指肠组织中的表达。通过免疫荧光共聚焦显微镜和流式细胞术，我们确定 MICA/B 主要在肠上皮细胞中位于细胞内。此外，我们在上皮内和固有层中均鉴定出 MICA/B(+)T 细胞。我们还在固有层中发现了 MICA/B(+)B 细胞、浆细胞和一些巨噬细胞。在严重肠病的黏膜组织中，MICA/B 的染色模式与细胞应激体外模型中发现的模式相似。在这些模型中，MICA/B 位于与活性 CD 肠病中观察到的氧化应激和内质网应激反应相关的应激颗粒中。我们的研究结果表明，CD 患者肠道黏膜中 MICA/B 的表达与黏膜稳态失调有关，应激反应在其中起积极作用。
