Pathophysiological role of CD1d in organ-specific inflammation

非MHC编码的CD1家族提供了一种不同于MHC I类或II类分子的新型脂质抗原呈递系统。而组1 CD1 （CD1a， CD1b和CD1c）在大鼠和小鼠中不存在，组2 CD1d在哺乳动物进化中保存，包括小鼠，大鼠，兔，羊和人类。CD1d分子在多种器官中表达，在肠上皮、肝细胞、表皮细胞中强烈表达，在胸腺细胞和血淋巴细胞中较少表达。从系统发育的角度来看，一些研究人员假设CD1d分子在各种哺乳动物免疫系统中具有相似的功能意义。然而，CD1d在炎症病理基础中的作用尚不完全清楚。我们发现，cd1反应性淋巴细胞在正常肝脏中富集，并在肝脏炎症状态下增殖。对动物模型和遗传性人类疾病（Wilson病）中铜超载的详细检查显示，携带不变性CDR3的NKT细胞可以作为严重（暴发性）肝炎的标志物。在动物模型中，这些细胞直接破坏肝细胞。另一方面，肺部轻度过敏性炎症性疾病的蘑菇植物工人经历Th2移位和先天炎症细胞激活，没有证据表明CD1d反应细胞和NKT细胞增加。当肺部状况变得严重（过敏性脑炎）时，细胞增加。这些结果表明CD1d自身反应细胞在炎症性疾病的进展中起关键作用。

The non-MHC-encoded CD1 family provides a novel lipid antigen-presenting system that is distinct from either MHC class I or class II molecules. Whereas the group 1 CD1 (CD1a, CD1b and CD1c) were absent in rats and mice, the group 2 CD1d has been conserved through mammalian evolution including mice, rats, rabbits, sheep, and humans. CD1d molecules are expressed by a wide variety of organs, appearing strongly in the intestinal epithelium, hepatocytes, epidermal cells, and to a lesser extent in thymocytes and hematolymphoid cells. From a phylogenetic standpoint, several investigators have hypothesized that CD1d molecules have a similar functional significance in various mammalian immune systems. However, roles of CD1d in pathological basis of inflammation is not fully understand. We find, that CD1d-reactive lymphocytes are enriched in the normal liver and propagated in its inflammatory condition of liver. Detailed examination of the copper overload in an animal model and inherited human disorder (Wilson disease) revealed that that invariant CDR3 bearing NKT cells can be used as a marker of severe (fulminant) hepatitis. In the animal model, these cells directly contribute destruction of hepatocytes. On the other hand, mushroom plant workers with mild allergic inflammatory disorder of the lung experience a Th2 shift and activation of innate inflammatory cells, no evidence of increase of CD1d reactive cells and NKT cells. When the lung status become severe (hypersensitive pneurnonitis), the cells are increased. These results suggest that CD1d self reactive cells play critical roles in progression of inflammatory disorders.