Laboratory of Molecular Medicine
Immunology of Innate Immune cells
Major histocompatibility complex
For the understanding of the mechanism by which innate immune cells distinguish self from non-self and prevent innate immune cell destruction of self.
The body of multicellular organisms, like us, is protected from invading pathogens by immune system. The Immune system consists of innate immune system and adaptive immune system. In the adaptive immune system, immune cells reactive with self are basically removed during their development process, however, the innate immune cells appears to lack such process, but prevent the self-reactive cells to attach normal self by means of inhibitory receptors that recognize self.
In our laboratory, we seek to reveal the ligands recognized by inhibitory receptors on innate immune cells and to regulate the innate immune system, especially inflammation, using antibodies against the inhibitory receptors on innate immune cells.
(1) Identification of myeloid cells that express each member of DCIR family molecules
Mouse DCIR family consists of four inhibitory receptors, DCIR1~4, and two activating receptors, DCAR1 and 2, while human DCIR family consists of one inhibitory receptor, DCIR, and one activating receptor, BDCA2. The genes for these receptors have been shown to be expressed in myeloid cells, which include macrophages, monocytes, neutrophils and eosinophils, however, expression of these receptors at protein levels remains to be examined. We established monoclonal antibodies, each of which specifically recognizes each member of the mouse DCIR family and are unveiling the expression of the DCIR family molecules in subpopulations of myeloid cells that exist in various organs.
(2) Examination of the function of DCIR2 using mice that genetically lack expression of DCIR2 ligands
We found that DCIR2 binds N-glycans with a unique structure called bisecting GlcNAc. However, the physiological role of DCIR2 recognition of the bisecting GlcNAc-containing N-glycans remains to be elucidated. We are investigating the question, using Mgat3-deficient mice that lacks high-affinity DCIR2 ligands, bisecting GlcNAc-containing N-glycans.
(3) Regulation of inflammation targeting inhibitory receptors on myeloid cells.
In various diseases that accompany inflammation, severe inflammation brings serious diseases. Myeloid cells play central roles in development of inflammation. We seek to develop new tools to control inflammatory diseases, targeting inhibitory receptors expressed on myeloid cells.