Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

Preliminary evaluation of adjuvant effects of cyclic dinucleotides ( CDN ) on immune responses to nasal spray influenza vaccine / 中华微生物学和免疫学杂志

Objective To analyze the immunostimulatory effects of cyclic dinucleotides ( CDN) on immune responses to a nasal spray influenza split virus vaccine and to evaluate its potential as a mucosal ad-juvant. Methods A H1N1 influenza split virus vaccine combined with different CDN was used for mouse immunization. Each mouse was intranasally immunized twice with 4. 5μg of hemagglutinin (HA) and 10μg of CDN with an interval of 21 d. Titers of hemagglutination inhibition ( HI) antibodies in serum, secretory IgA ( sIgA) in bronchoalveolar lavage fluid and IgG in serum were detected 21 d after the last immunization. Immunostimulatory activities of different CDN were compared. Effects of cyclic di-GMP ( c-di-GMP) and ch-itosan (CSN) on the immunogenicity of H1N1 and H7N9 influenza split vaccines were analyzed and com-pared. H1N1 influenza split vaccine combined with c-di-GMP or CSN was used to immunize mice. Three weeks after the last immunization, these mice were challenged with 10 times the median lethal dose ( LD50 ) of A/Puerto Rico/8/34 (H1N1) influenza virus. Survival rates of the mice were observed for 14 d. Results All three CDN induced high levels of HI antibodies and IgG in serum and sIgA in BALF. HI antibody sero-conversion rates were also higher than those of the control groups. c-di-GMP was superior to CSN in enhan-cing the immunogenicity of H1N1 and H7N9 antigens as higher titers of HI antibodies in serum and sIgA in BALF were induced. Conclusions CDN could enhance the immunogenicity of influenza antigens with better efficacy than CSN adjuvant.