Systemically derived large intestinal CD4+ Th2 cells play a central role in STAT6-mediated allergic diarrhea
Systemically derived large intestinal CD4+ Th2 cells play a central role in STAT6-mediated allergic diarrhea
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DOI：
10.1172/jci8490
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发表时间：
2000-07-01
影响因子：
15.9
通讯作者：
Kiyono, H
中科院分区：
文献类型：
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作者：
Kweon, MN;Yamamoto, M;Kiyono, H
系统性致敏的BALB/c小鼠在反复口服卵清蛋白（OVA）后出现严重腹泻。组织学分析表明，腹泻小鼠的大肠而非小肠中有大量嗜酸性粒细胞和肥大细胞浸润。有趣的是，大肠中的CD4(+)αβ T细胞高水平分泌白细胞介素 - 4（IL - 4）和白细胞介素 - 13（IL - 13）。经相同处理的STAT6基因敲除小鼠未出现OVA诱导的腹泻。此外，用单克隆抗IL - 4抗体治疗BALB/c小鼠可防止过敏性腹泻的发生。一项过继转移研究表明，系统性致敏的脾CD4(+) T细胞在口服OVA后优先募集到大肠。这些结果有力地表明，大肠中来源于全身的CD4(+)αβ T细胞通过STAT6信号转导在Th2介导的肠道过敏性疾病的发病中起关键作用。
Systemically primed BALB/c mice developed severe diarrhea after repeated oral administration of ovalbumin (OVA). Histological analysis demonstrated that dramatic infiltration of eosinophils and mast cells occurred in the large intestine but not in the small intestine of mice with diarrhea. Interestingly, CD4(+) alpha beta T cells of the large intestine secreted IL-4 and IL-13 at high levels. Identically treated STAT6 gene-disrupted mice failed to develop OVA-induced diarrhea. Further, treatment of BALB/c mice with monoclonal anti-IL-4 antibody prevented the development of allergic diarrhea. An adoptive transfer study showed that systemically primed splenic CD4(+) T cells were preferentially recruited into the large intestine upon exposure to oral OVA. These results strongly suggest that systemically derived CD4(+) alpha beta T cells of the large intestine play a critical role in the onset of Th2-mediated intestinal allergic disorders via STAT6 signal transduction.