10Ly6CLy6GF4/80TCRTCRCD8CD11cTCRTCRCD8Research subjectResearch subjectOutlook for students after graduationOutlook for students after graduation?Transcription factors for switching various genes in immune cells on/off in a timely fashion. ? Signal transduction molecules that convey various intracellular signals for the functions of immune cells.Outlook for researchToday, in the field of immunology, growing numbers of new therapies are brought forth for cancers and immune-related diseases such as rheumatoid arthritis. Also uncovered recently is the contribution of the immune system to the regulation of good relationship between our health and bacteria living in the gut and skin. Deeper understanding of the immune system will hence provide us with valuable hints on not only improvement of disease diagnosis and therapies, but also better life styles to keep ourselves healthy.By acquiring basic knowledge and gaining practical skills in immunology in our laboratory, graduates are expected to be clinicians who have scientist’s eyes and continuously ask ‘why’ and ‘how’ also in clinics. ?Investigation of a mechanism of the carcinogenesis?Elucidation of cancer metastasis?Functional analysis of anti-metastatic cellsOutlook for researchToday, in a cancer therapy, especially against metastatic cancer, anticancer drug treatment was employed. Our mouse study revealed that a subtype of innate immune cells have an-ti-metastatic abilities. These cells cancel the premetastatic soil formation and attack against metastatic cells. We are considering clinical application based on our research data.Through the cancer study, you can extend your views of various fields. It will give you great activity in many kinds of area, such as healthcare, education, public administration, research, and so on.Fig.1 Analysis of immune cell populations in the spleen in mice, separated by 4 param-eter flowcytometry technique. (yellow: neutrophils, light blue: monocytes, light green: macrophages, pink: dendritic cells) .Fig.2 T lymphocyte subpopulations in the intestinal epithelia in mice made deficient in a gene (yellow: TCRαβ T cells, light blue: TCRγδ T cells). Note that TCRαβ T cells are absent in the mutant mice (right). Pre-metastatic permeability controlled by innate immune system. Initially, tumor-de-rived CCL2 stimulates CCR2 in the pre-metastatic lungs. Next, this induces S100A8-SAA3 pathway and stimulates TLR4/MD2 cycles. Those cascades further promote hyper-permeability and inflammation.Detection of the focal region in tumor-bearing mice with the permeability phenomena. LLC and E0771, breast cancer cells lines, were used to generate tumor-bearing mice. Note that some hyper-permeability area made by Evans Blue dye injection, was found in tumor-bearing mouse lung.Wild-type miceMutant miceSummary of ActivityOne of our body’s activities essential to live healthy is the immune system. This system has to work properly, and with too weak immunity we are vulnerable to infections and cancers, while too strong immunity leads to allergies and autoimmune diseases. In order to understand how the immune system works, our laboratory pursues the mechanisms by which to generate various cells in the immune system and to make them work appropriately. These studies will contribute to the prevention and cure of various diseases.Summary of ActivityOur efforts are directed to reveal molecular mechanisms of tumorigenesis and tumor metastasis. By using tumor-bearing mouse model system, we have de-termined that primary tumor elicits an inflammatory reaction in a remote organ before metastasis, which is termed as “premetastatic soil”. This inflammatory reaction enhances vascular permeability, and recruitment of immunosuppressor cells and/or circulating tumor cells, these factors increase the risk of tumor me-tastasis. Thus, we consider that controlling the premetastatic phase is an import-ant step to prevent tumor metastasis.How the immune system is built up and works rightlySearching a key for suppressing cancer metastasisMolecular and （Chief: Prof. Shinsuke Taki）Cellular ImmunologyBiochemistry and Molecular Biology（Chief: Prof. Sachie Hiratsuka）
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