Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Molecular Sciences  

Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient’s survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules.

DOI： 10.3390/ijms25137346

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PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Medical Virology  

Influenza A virus (IAV) infection causes respiratory disease. Recently, infection of IAV H5N1 among mammals are reported in farmed mink. Therefore, to discover antivirals against IAV, we screened a compound library by using the RNA-dependent RNA polymerase (RdRp) assay system derived from H5N1 IAV including a drug-resistant PA mutant (I38T) and a viral polymerase activity enhancing PB2 mutant (T271A). Upon screening, we found vidofludimus can be served as a potential inhibitor for IAV. Vidofludimus an orally active inhibitor for dihydroorotate dehydrogenase (DHODH), a key enzyme for the cellular de novo pyrimidine biosynthesis pathway. We found that vidofludimus exerted antiviral activity against wild-type and drug-resistant mutant IAV, with effective concentrations (EC<inf>50</inf>) of 2.10 and 2.11 μM, respectively. The anti-IAV activity of vidofludimus was canceled by the treatment of uridine or cytidine through pyrimidine salvage synthesis pathway, or orotic acid through pyrimidine de novo synthesis pathway. This indicated that the main target of vidofludimus is DHODH in IAV RdRp expressing cells. We also produced recombinant seasonal IAV H1N1 virion and influenza B virus (IBV) RdRp assay system and confirmed vidofludimus also carried highly antiviral activity against seasonal IAV and IBV. Vidofludimus is a candidate drug for the future threat of IAV H5N1 infection among humans as well as seasonal influenza virus infection.

DOI： 10.1002/jmv.29372

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PubMed