Modifying toll-like receptor 9 signaling for therapeutic use.
Toll-like receptor (TLR) 9 recognizes synthetic oligodeoxynucleotides (ODN) containing unmethylated deoxycytidyl-deoxyguanosine (CpG) motifs and mimics the immunostimulatory activity of bacterial DNA. Both innate and adaptive immune systems are activated through TLR9 signaling and thus its synthetic agonists or inhibitors have potential significance as a target for therapeutic use in immunological disorders. Interestingly, TLR9 found in the dendritic cells and B cells produce differential outcome in response to structurally distinct CpG-ODNs. While one class of CpG-ODN activates B cells and produce immunoglobulin, other can either redirect plasmacytoid dendritic (pDC) cells to secrete high level of IFNalpha or myeloid dendritic cells (mDC) to produce Th1-like cytokines and chemokines necessary for asthma control. This review focuses on potential use of various synthetic CpG to modify TLR9 signaling for therapeutic treatment of multiple diseases including cancer, asthma, allergy and systemic lupus erythematosus (SLE).
Bhattacharjee
Rabindra N
RN
Akira Innate Immunity Project, Explanatory Research for Advanced Technology (ERATO), Japan Science and Technology Agency, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Akira
Shizuo
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy; D001402:B-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D003845:Deoxycytosine Nucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007154:Immune System Diseases / Q000188:drug therapy; D007073:Immunoglobulin E / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000378:metabolism / Q000502:physiology*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D018925:Chemokines; D016207:Cytokines; D003845:Deoxycytosine Nucleotides; D051217:Toll-Like Receptor 9; D007073:Immunoglobulin E