EAPSI: Investigating Specific Immune Response Genes Induced by a Cell-To-Cell Signaling Molecule

在过去的几十年里，免疫学的进步导致了有效的癌症免疫疗法，被《科学》杂志评为2013年的“年度突破”。以前无法治愈的癌症现在对免疫疗法有了反应。尽管有这些令人信服的结果，但更多关于抗肿瘤免疫的基础研究可以学到很多东西。特别是，目前尚不清楚如何通过周围细胞和免疫细胞之间的相互作用最初检测到新出现的异常细胞并阻止其进一步增殖。我们之前已经确定了将免疫细胞招募到肿瘤中的细胞间信号分子。鉴定出的分子白介素- 17d （IL-17D）是一种已知的信号分子，在鱼类和牡蛎等无脊椎动物中对病原体进行炎症反应。本项目将研究IL-17D对哺乳动物细胞基因活化和基因修饰的影响。与九州大学表观遗传学专家Hiroyuki Sasaki博士合作，该项目将揭示IL-17D信号如何介导免疫细胞激活的新见解。该项目将通过表征一种涉及炎症的保守分泌蛋白诱导的基因来推进免疫学领域的知识。这项研究将在九州大学进行，由佐佐木博之教授负责。该项目利用RNA-seq和亚硫酸盐测序分析研究了IL-17D刺激细胞的整体基因表达和表观遗传修饰。该项目研究了1)IL-17D诱导的免疫应答基因和2)长时间IL-17D刺激在分化和转化细胞类型中的表观遗传变化。该项目的成功完成将导致对IL-17D信号如何介导转化细胞的监视的详细了解。该项目的结果将有助于开发有效免疫疗法所需的基础研究。该奖项隶属于东亚和太平洋暑期研究所项目，由美国国家科学基金会和日本科学促进会共同资助，支持一名美国研究生进行暑期研究。

Over the past few decades, advances in immunology have led to efficacious immune therapies for cancer, recognized as the "Breakthrough of the Year" by Science Magazine in 2013. Previously incurable cancers are now responding to immune therapies. Despite these compelling results, much can be learned by more basic research studies on anti-tumor immunity. In particular, it is not well known how emerging aberrant cells are initially detected and prevented from proliferating further through the interaction between the surrounding cells and the immune cells. We have previously identified the cell-to-cell signaling molecule that recruits immune cells into tumors. The identified molecule, interleukin-17D (IL-17D) is known as a signal molecule that carries out inflammation against pathogens in fish and also in invertebrates such as oysters. This project will investigate the impact of IL-17D on the gene activation and gene modification in cells of mammalian origin. In collaboration with Hiroyuki Sasaki, MD, PhD, an expert on epigenetics at Kyushu University, the project will uncover new insights into how IL-17D signals to mediate immune cell activation.The project will advance the knowledge in the field of immunology by characterizing the genes induced by a conserved secreted protein involved in inflammation. This research will be carried out at Kyushu University under Professor Hiroyuki Sasaki. The project investigates the global gene expression and epigenetic modifications in cells stimulated with IL-17D using RNA-seq and bisulfite sequencing analyses. The project investigates 1) the immune response genes induced in response to IL-17D and 2) epigenetic changes from prolonged IL-17D stimulation in differentiated versus transformed cell types. Successful completion of this project will lead to detailed understanding on how IL-17D signals to mediate surveillance of transformed cells. Results from this project will contribute towards the basic research needed to develop efficacious immune therapies.This award under the East Asia and Pacific Summer Institutes program supports summer research by a U.S. graduate student and is jointly funded by NSF and the Japan Society for the Promotion of Science.