Immunomodulation by IPSE/alpha-1, an excretory/secretory protein from Schistosoma mansoni eggs

慢性血吸虫病的特点是由血吸虫卵引起的强烈的抗炎免疫反应。我们之前已经鉴定出一种血吸虫卵产物IPSE/ α -1，它能触发嗜碱性细胞释放IL-4和IL-13。值得注意的是，这些细胞因子通过减少促炎细胞因子的释放和诱导抗炎选择性活化的巨噬细胞（AAMs）来抑制炎症。由于嗜碱性粒细胞迁移到寄生虫感染的组织并参与诱导aam，我们提出通过触发嗜碱性粒细胞IL-4 IPSE/ α -1可以抑制炎症过程。我们实验室未发表的数据支持这一假设。有趣的是，IPSE/ α -1活化的嗜碱性粒细胞的抗炎作用被TLR配体放大。我们计划系统地研究IPSE/ α -1的影响：i)在细胞共培养系统中对促/抗炎细胞因子释放的影响，ii)对除嗜碱性细胞外的免疫细胞的影响，包括介质释放和功能后果，以及iii)对慢性实验性结肠炎的保护作用。我们希望我们的研究将有助于开发治疗慢性炎症（如过敏和自身免疫性疾病）的新策略。

Chronic schistosomiasis is characterized by a strong anti-inflammatory immune response caused by schistosome eggs. We have earlier identified a schistosome egg product, IPSE/alpha-1, that triggers basophils to release IL-4 and IL-13. Notably, these cytokines inhibit inflammation by re-ducing pro-inflammatory cytokine release and by inducing anti-inflammatory alternatively activated macrophages (AAMs). Since basophils migrate to parasite-affected tissues and are involved in inducing AAMs, we propose that by triggering basophil IL-4 IPSE/alpha-1 turns down inflammatory processes. Unpublished data from our lab support this hypothesis. Interestingly, the anti-inflammatory effect of IPSE/alpha-1-activated basophils is amplified by TLR ligands. We plan to systematically investigate the effects of IPSE/alpha-1: i) on pro-/anti-inflammatory cytokine release in cell co-culture systems, ii) on immune cells beyond basophils including mediator release and functional consequen-ces, and iii) regarding protection against chronic experimental colitis. We expect our study will help develop new strategies for treating chronic inflammations such as allergy and autoimmune diseases.