Academic Journal
ZBP1 and IFI16: novel innate sensors and inflammation regulation under infection stress.
| Τίτλος: | ZBP1 and IFI16: novel innate sensors and inflammation regulation under infection stress. |
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| Συγγραφείς: | Lu C; The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Xu B; The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China., Xiong Y; The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Sep 22; Vol. 17, pp. 1869593. Date of Electronic Publication: 2026 Sep 22 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Phosphoproteins*/immunology , Phosphoproteins*/metabolism , Phosphoproteins*/chemistry , RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/immunology , RNA-Binding Proteins*/chemistry , Inflammation*/immunology , Inflammation*/metabolism , Nuclear Proteins*/immunology , Nuclear Proteins*/metabolism , Nuclear Proteins*/chemistry , Infections*/immunology , Infections*/metabolism , Immunity, Innate*, Humans ; Animals ; Innate Immunity Recognition ; Signal Transduction |
| Περίληψη: | The innate immune system is the first line of defense against infection, using pattern recognition receptors to sense pathogens and abnormal host-derived nucleic acids. Among these, Z-DNA-binding protein 1 (ZBP1) and interferon gamma-inducible protein 16 (IFI16) are two important nuclear and cytosolic nucleic acid sensors attracting recent attention. These sensors play key roles in detecting abnormal nucleic acids from viruses, bacteria, and damaged host cells. They trigger downstream innate immune responses to regulate inflammation. Despite much progress, key questions remain about how they are exactly activated under infection stress, the complexity of their signaling networks, and their dual roles in protective immunity and pathological inflammation. This review summarizes the structural features of ZBP1 and IFI16, how they recognize ligands, and their interactions with key signaling molecules (including RIPK1, RIPK3, MLKL, and caspase-1). We then emphasize cell fate decisions mediated by these sensors. Especially, ZBP1 is the core upstream regulator of PANoptosis (an integrated form of programmed cell death combining pyroptosis, apoptosis, and necroptosis via the PANoptosome complex), alongside classical cell death pathways. In addition, we review recent advances to highlight functional roles of ZBP1 and IFI16 in herpesvirus, influenza virus, and bacterial infections, and their dysregulation in autoimmune diseases. For IFI16, human studies and murine homolog-based evidence are analyzed. Further we review unique and overlapping functions, including a comparison with other canonical nucleic acid sensors (e.g., cGAS, AIM2, RIG-I) and analyze the ADAR1-ZBP1 axis in self-nonself nucleic acid discrimination. We cover the therapeutic potential of targeting ZBP1- and IFI16-mediated pathways for anti-inflammatory and anti-infective strategies and provide a balanced analysis of developmental challenges, potential toxicity, and risks of impaired immune surveillance. (Copyright © 2026 Lu, Xu and Xiong.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: IFI16; PANoptosis; ZBP1; infection; inflammation regulation; innate immunity; nucleic acid sensor; pyroptosis |
| Substance Nomenclature: | 148998-64-5 (IFI16 protein, human) 0 (Phosphoproteins) 0 (RNA-Binding Proteins) 0 (ZBP1 protein, human) 0 (Nuclear Proteins) |
| Entry Date(s): | Date Created: 20261007 Date Completed: 20261007 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| PubMed Central ID: | PMC13639999 |
| DOI: | 10.3389/fimmu.2026.1869593 |
| PMID: | 42840615 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1869593 |