Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice
Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice
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DOI：
10.1002/eji.200324833
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Weinstock, JV
中科院分区：
文献类型：
--
作者：
Elliott, DE;Setiawan, T;Weinstock, JV
炎症性肠病（IBD）在工业化国家普遍存在，但在欠发达国家很少见。蠕虫在欠发达国家很常见，可能会诱导免疫调节回路预防炎症性肠病。给予吡罗昔康的IL-10(-/-)小鼠出现严重且持续的结肠炎。结肠炎 IL-10(-/-) 小鼠的固有层单核细胞释放 IFN-γ 和 IL-12。抗IL-12单克隆抗体可以部分阻断正在进行的吡罗昔康诱导的结肠炎，这表明炎症至少部分依赖于IL-12。 Heligmosomoides polygyrus（一种肠道蠕虫）在经吡罗昔康治疗的结肠炎 IL-10(-/-) 小鼠中定植，可抑制已形成的炎症并抑制粘膜 IL-12 和 IFN-γ 的产生。 H. polygyrus 增加了粘膜 IL-13 的产生，但不增加 IL-4 或 IL-5 的产生。将携带 H.polygyrus 的 IL-10(-/-) 动物的肠系膜淋巴结 (MLN) T 细胞转移到结肠炎 IL-10(-/-) 受体中可抑制结肠炎。来自无蠕虫小鼠的 MLN T 细胞却没有。 Foxp3 (scurfin) 驱动调节性 T 细胞功能。 H. polygyrus 增强了具有调节活性的 MLN T 细胞中 Foxp3 mRNA 的表达。这表明 H. polygyrus 部分通过阻断粘膜 Th1 细胞因子的产生来抑制正在进行的 IL-10(-/-) 结肠炎。炎症的消退与 IL-13 产生的增加有关，并且可以通过 MLN T 细胞过继转移。
Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells.