P18 Unc93 homolog B1 restricts systemic lethal inflammation by orchestrating TLR7 and TLR9 response Ryutaro HIF inhibitors Fukui1, Shin Ichiroh Saitoh1, Atsuo Kanno1, Masahiro Onji1, Takuma Shibata1,2, Akihiko Ito4, Morikazu Onji5, Mitsuru Matsumoto6, Shizuo Akira7,8, Nobuaki Yoshida3, Kensuke Miyake1,2 1Division of Infectious Genetics, Division of Microbiology and Immunology, The Institute of Health-related Science, The University of Tokyo, 4 6 1 Web page 27 of 54 Shirokanedai, Minatoku, Tokyo 108 8639, Japan, 2Laboratory of Innate Immunity, The Institute of Healthcare Science, The University of Tokyo, 4 6 1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan, 3Laboratory of Developmental Genetics, Center for Experimental Medication and Programs Biology, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minatoku, Tokyo 108 8639, Japan, 4Department of Pathology, Faculty of Medication, Kinki University, Osaka 589 8511, Japan, 5Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime 791 0295, Japan, 6Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770 8504, Japan, 7Laboratory of Host Defense, Globe Premier Global Immunology Frontier Exploration Center, Osaka 565 0871, Japan, 8Department of Host Defense, Research Institute for Microbial Diseases, Osaka HSP90 activation University, Osaka 565 0871, Japan Arthritis Study & Therapy 2012, 14 18 Nucleotide sensing TLRs recognize pathogen derived nucleic acids and trigger immune response.

Because of the highly conserved structure of nucleic acids, these TLRs have risk to recognize host derived Eumycetoma nucleic acids and induce autoimmune disease, therefore it is imhigh throughput screening portant to clarify the mechanisms and control the response. We found that the responses of TLR7 and TLR9 are balanced reciprocally, and Unc93 homolog B1 is a key molecule for this balancing system. Unc93B1 is known as an essential molecule for TLR3, TLR7, and TLR9 responses, and the function depends on its C terminal region. The balancing function of Unc93B1 is located on 34th aspartic acids from N terminal, and alanine mutant Unc93B1 up regulates TLR7 response and down regulates TLR9 response. It is reported that TLR7 or TLR9 response contributes to some kinds of autoimmune disease and TLR7 overexpressed mice develop SLE like autoimmune disease.