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Study on immunoreceptors involved in the pathogenesis of intractable diseases

 Immunity is a defense system that discriminates non-self, such as pathogens, allergen, cancer, and transplanted organs, from self and eliminates non-self. Immunoreceptors are expressed on the cell surface of various immune cells, transmit a signal into cells, and regulates immune cell activation. They trigger immune responses as a result of binding to their respective ligand expressed on other immune cells or soluble proteins such as cytokines or growth factors. Thus, immunoreceptors play an important role in the development of intractable diseases, for which immune responses are responsible. To overcome the intractable diseases, it is required to clarify the function of and control immunoreceptors.
 Our group has been trying to identify novel immunoreceptors that are involved in the pathogenesis of intractable diseases and clarify their function by using animal disease models for more than 20 yeas and pulling the research field in the world.
  We discovered DNAM-1 that is involved in cytotoxic activity by killer lymphocytes in 1996, and thereafter clarified that DNAM-1 suppressed cancer development. These results have provided the formal evidence for the theory “Cancer immune surveillance” proposed by Dr. Burnet, who won Novel prize for Medicine and Physiology in 1960, and clarified its molecular mechanism. We also discovered Fcα/μR as an Fc receptor for IgM in 2000 that had not been identified for long time regardless of much efforts by many researchers, and thereafter clarified that Fcα/μR is involved in immune responses against pathogens covered by polysaccharides such as Streptcoccus pneumoniae. These studies are expected to lead to the development of an effective vaccination by targeting Fcα/μR. Furthermore, we discovered MAIR-I and MAIR-II expressed on mast cells and dendritic cells in 2003, and thereafter clarified that these molecules regulate sepsis caused by bacterial infection and inflammatory bowel diseases. In 2010, we found that Allergin-1 expressed on mast cells strongly inhibit the release of chemical mediators such as histamine from mast cells, which is common phenomenon in any type of allergic diseases. These results are expected to the development of a novel therapy for allergic diseases, including seasonal rhinitis, asthma, atopic dermatitis, food allergy and anaphylaxis, which more than 30% people suffered from all over the world.


DNAM-1 (CD226)
Allergin-1(Allergy inhibiotry receptor-1、Allargin-1)