Judd L M, Gleeson P A, Toh B H, van Driel I R
Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Melbourne, Victoria, Australia 3181.
Am J Physiol. 1999 Jul;277(1):G209-18. doi: 10.1152/ajpgi.1999.277.1.G209.
We have investigated the underlying basis of the lesion in murine autoimmune gastritis, a model of the human disease pernicious anemia. The disease is mediated by T lymphocytes and characterized by selective depletion of parietal and zymogenic cells from the gastric unit (gland) together with gastric epithelial cell hyperplasia. The gastric units of gastritic stomachs contained 2.3-fold more cells than normal and accumulated rapidly dividing, short-lived gastric epithelial stem cells and mucous neck cells. Most of these immature cells failed to differentiate into end-stage cells but rather appeared to die by apoptosis. We also found no correlation between anti-parietal cell autoantibody titers and the degree of gastric pathology, providing further evidence that autoantibodies do not play a direct role in the pathogenesis of gastritis. Taken together, the normal developmental pathways of the gastric mucosa are disrupted in autoimmune gastritis, resulting in an amplification of immature cell types. The differentiation of these immature cells appears to be blocked, contributing to depletion of end-stage cells. This scenario provides an explanation for depletion of not only parietal cells but also zymogenic cells even though they are not directly targeted by the immune system.
我们研究了小鼠自身免疫性胃炎（一种人类恶性贫血疾病的模型）中病变的潜在基础。该疾病由T淋巴细胞介导，其特征是胃单位（腺体）中的壁细胞和泌酸腺细胞选择性耗竭，同时伴有胃上皮细胞增生。胃炎胃的胃单位所含细胞比正常情况多2.3倍，并积累了快速分裂、寿命短的胃上皮干细胞和黏液颈细胞。这些未成熟细胞大多未能分化为终末细胞，而是似乎通过凋亡死亡。我们还发现抗壁细胞自身抗体滴度与胃部病理程度之间没有相关性，这进一步证明自身抗体在胃炎发病机制中不发挥直接作用。综上所述，自身免疫性胃炎中胃黏膜的正常发育途径被破坏，导致未成熟细胞类型扩增。这些未成熟细胞的分化似乎受阻，导致终末细胞耗竭。这种情况不仅解释了壁细胞的耗竭，也解释了泌酸腺细胞的耗竭，尽管它们并非免疫系统的直接靶点。
