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35ACHIEVEMENTPUBLICATIONCold Spring Harbor Symposium of Asia. 2018 SepThe 11th APCCN and the 14th CNSC. 2019 SepSugahara H, Okai S, Odamaki T, Wong CB, Kato K, Mitsuyama E, Xiao JZ, Shinkura R. Decreased Taxon-Specific IgA Response in Relation to the Changes of Gut Microbiota Composition in the Elderly. Front Microbiol. 2017 Sep 12;8:1757. DOI:10.3389/fmicb.2017.01757SHINKURAREIKOMD (1986) KYOTO UNIVERSITYPH.D. (1996) KYOTO UNIVERSITYHHMI RESEARCH ASSOCIATE (1999) CHILDREN'S HOSPITAL /HARVARD MEDICAL SCHOOLASSISTANT AND ASSOCIATE PROFESSOR(2004) KYOTO UNIVERSITYPROFESSOR (2010) NAGAHAMA INSTITUTE OF BIO-SCIENCE AND TECHNOLOGYPROFESSOR (2016) NARA INSTITUTE OF SCIENCE AND TECHNOLOGYPROFESSOR (2017) INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, THE UNIVERSITY OF TOKYOPROFESSOR (2018) IQB / INSTITUTE FOR QUANTITATIVE BIOSCIENCES, THE UNIVERSITY OF TOKYO●MEMBER■ PROFESSOR :SHINKURA REIKO■ RESEARCH ASSOCIATE :MORITA NAOKI■ RESEARCH ASSOCIATE : MORI TOMOYUKI■ PROJECT RESEARCHER : MORITA KYOKO■ TECHNICAL STAFF :TAMANO RYUTAROhe immune response has evolved to protect us from pathogenic infectious agents and toxic foreign substances. In acquired immune response, antigen stimulation of B cells induces two distinct genetic alterations in the immunoglobulin (Ig) loci: somatic hypermu-tation (SHM) and class switch recombination (CSR), both of which require an enzyme, activation-induced cytidine deaminase (AID). AID plays a crucial role in host defense but it introduces DNA cleavage into Ig loci and aberrantly into non-Ig loci causing lympho-ma. Our aim is to answer‘ how AID’s activity targets Ig loci specifically’ and to understand the precise molecular mechanism of SHM and CSR.We aim at applying the findings of our basic research to practical medicine.1. Mechanism of gut microbial regulation by intestinal IgA Recently dysbiosis (gut commensal microbial imbalance) is frequently reported to be associated with illnesses such as inflammato-ry bowel disease (IBD), obesity, cancer, etc. We found that the high-affinity intestinal IgA produced by SHM is important to control non-pathogenic gut bacteria as well as pathogens. We are analyzing the bacterial target molecule for each monoclonal IgA. We aim at the development of therapeutic IgA antibody to modulate gut microbiota leading to symbiosis (balanced hostmicrobial relationship in gut).2. Search for IgA CSR inducerWe focus on searching a novel IgA CSR inducer, which may drive IgA CSR instead of IgE CSR at mucosal surface, helping prevent allergy, as well as enhance the mucosal immunity.TSYMPOSIUMSYMPOSIUM(1) IgA oral treatment is a potential remedy not only for inflammatory bowel disease but also extra-intestinal disorders, acting through restoration of the host-microbial symbiosis. (2) Selective CSR to IgA can prevent allergic response as well as enhance mucosal defense against a same antigen.