Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou, China.
UMR 7355 Université-CNRS INEM, Orléans, France and IDM, University of Cape Town, Cape Town, South Africa.
Front Immunol. 2019 Apr 18;10:702. doi: 10.3389/fimmu.2019.00702. eCollection 2019.
Oral infection (30 cysts of 76K strain) induces acute lethal ileitis in sensitive C57BL/6 (B6) mice with increased expression of IL-33 and its receptor ST2 in the ileum. Here we show that IL-33 is involved in ileitis, since absence of IL-33R/ST2 attenuated neutrophilic inflammation and Th1 cytokines upon infection with enhanced survival. Blockade of ST2 by neutralizing ST2 antibody in B6 mice conferred partial protection, while rmIL-33 aggravated ileitis. Since IL-22 expression further increased in absence of ST2, we blocked IL-22 by neutralizing antibody, which abrogated protection from acute ileitis in ST2 deficient mice. In conclusion, severe lethal ileitis induced by oral infection is attenuated by blockade of ST2 signaling and may be mediated in part by endogenous IL-22.
口腔感染（76K 株 30 个囊泡）可诱导易感性 C57BL/6（B6）小鼠发生急性致死性回肠炎，回肠中 IL-33 及其受体 ST2 的表达增加。在这里，我们表明 IL-33 参与了回肠炎，因为缺乏 IL-33R/ST2 可减轻感染后中性粒细胞炎症和 Th1 细胞因子，并提高存活率。在 B6 小鼠中用中和 ST2 抗体阻断 ST2 可提供部分保护，而 rmIL-33 则加重回肠炎。由于缺乏 ST2 时 IL-22 的表达进一步增加，我们用中和抗体阻断 IL-22，这消除了 ST2 缺陷小鼠急性回肠炎的保护作用。总之，口腔感染诱导的严重致死性回肠炎可通过阻断 ST2 信号而减轻，其部分机制可能是通过内源性 IL-22 介导的。
