Our research focuses are how constituents of innate immunity and adaptive immunity distinguish self from non-self entity and the cross-talk between the two arms. Further, we aim to elucidate the roles of immune cells in tumor micro-environment.
A. Host-pathogen interaction/Innate immune signaling
This research topic is to elucidate molecular mechanisms by which innate immune system senses the invasion of host by pathogenic microorganisms, decodes the pattern associated with them, transforms it to an information signal(s), which triggers a signal cascade(s) that leads to activation of adaptive immune system. To reveal the intricate survival race between a host and a pathogen, and to contribute to the development of better therapeutic agents not only against intracellular pathogens but also against tumors, our study is currently focusing on the cellular and molecular mechanism for cGAS-STING mediated cytosolic sensing of DNA.
B. Hematopoiesis: Identification of myeloid cell subsets and elucidation of their development and differentiation process
The immune response is mediated by numerous cell types and their effector molecules, and accompanied by inflammatory responses, which are featured by the infiltration of myeloid cells to the lesion. These infiltrating myeloid cells cooperate with T cells and other immune cells and play critical roles in many steps of immune response. They are comprised of many different subsets. However, their functional contribution in the physiological and pathological condition remains to be determined in live animals. Therefore, accurate identification of the cells that are responsible in whole animals is critical to target the culprits. We are working identification of cells in the most sophisticated myeloid network encompassing dendritic cells, monocytes, macrophages, neutrophils and basophils, and determination of their precursors. By combining multiparametric flow cytometric analysis and transcriptome analysis, new lineage determinants of various subtypes are being revealed, which will facilitate generating in vivo tools that allow us to track and delete various myeloid cell subsets, thereby elucidating their in vivo roles.
C. Interplay between myeloid cells and T cells
T helper (Th) cells occupy a central position in orchestrating the diverse cell types that mediate host immunity to infections or tumors. T helper cells have been functionally classified into three major subtypes, Th1, Th2 and Th17, based on the types of immune molecules, called cytokines, that each subtype secretes. Th cell differentiation to each subset is determined by integration of communication between T cells and myeloid cells. Although many factors have been known to affect differentiation of Th1 and Th17, the initial cues for Th2 differentiation and the responsible myeloid cells remain unknown. We are investigating types of myeloid cells and molecular machinery involved in this process by tracing Th differentiation in cytokine reporter animals where the production of cytokines can be visualized in live animals.
D. Elucidation of the roles of immune cells in tumor microenvironment
Recently much attention has been paid to the association of inflammation with oncogenesis and tumor progression. We are studying the immune cells within the tumor micro-environment and their progenitor cells to reveal the cross-regulation between the tumor and immune cells, finding a key(s) to unlink them.