研究幽門螺旋桿菌熱緊迫蛋白60的序列對誘發宿主Treg細胞增加的影響及機制

Abstract

幽門螺旋桿菌於1980年代末期被發現以來，即成為胃腸科疾病及胃癌成因的重要研究課題。此菌 已被證實可造成人類胃上皮細胞的破壞、癌變以及抑制宿主免疫系統等現象。在本實驗室的研究中發 現，幽門螺旋桿菌的熱迫性蛋白60（HpHsp60）可使巨噬細胞產生較高量之IL-10及TGF-β以及多種發 炎性細胞激素、促使腫瘤細胞遷移能力及血管新生成能力增加。此外，本實驗室先前之研究結果亦指 出，HpHsp60具有誘發調控性T細胞（induced regulatory T cells, iTregs)增生的功能；而調控性T細胞已 被認定對於宿主免疫反應的抑制扮演重要的角色。我們推測幽門螺旋桿菌可能藉由Hsp60引發調控性T 細胞的增生，而對宿主免疫系統產生的抑制作用，故於本計劃將進一步研究HpHsp60引發調控性T細 胞增生的機制。本研究室預計探討幽門螺旋桿菌之Hsp60序列中具誘發調控性T細胞增生功能的區域。 是以本計畫之主要目的為：(1) 探討幽門螺旋桿菌Hsp60分子誘發Treg細胞產生之活性位置。(2) 探討 HpHsp60刺激後的巨噬細胞藉由何種機制使Treg生成增加。希望藉此研究能提供有用的資訊於未來有 利於發展藥物或疫苗以治療幽門螺旋桿菌引起的相關疾病。

Helicobacter pylori (H. pylori, Hp) has become an important issue in the field of gastrointestinal disease and the development of gastric cancer since its discovery in late 1980’s. It has been confirmed that Hp can damage human gastric epithelial cells, cause oncogenesis and suppress host’s immunity. In our previous studies, we found that H. pyori heat shock protein 60 (HpHsp60) could induce macrophage to increase the high expression of IL-10, TGF-β, and other proinflammatory cytokines. In addition, HpHsp60 also enhanced the abilities for migration of tumor cell and angiogenesis. Furthermore, HpHsp60 could induce the generation of regulatory T cell (Tregs). Tregs are considered to be an important factors involved in the suppression of host’s immune response. In this plan, we are going to investigate the mechanisms of how the HpHsp60 induce the generation of Tregs. The goads in this plan are: (1) to study the effective sequence of the HpHsp60 for the induction or function of Treg cell, (2) to investigate whether the HpHsp60-stimulated macrophage or its secretary cytokines can affect the induction or function of Treg cell. We hope these results can provide useful information to develop drug or vaccine for the therapy of H. pylori-induced diseases.