Evidence map›Paper›PMID 42840615›Full record

ReviewFrontiers in immunology2026

ZBP1 and IFI16: novel innate sensors and inflammation regulation under infection stress.

Chengbin Lu, Benmo Xu, Yu Xiong

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Chengbin Lu *The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Benmo Xu *The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Yu Xiong *The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Immunity, InnateInfectionsInflammationNuclear ProteinsPhosphoproteinsRNA-Binding ProteinsAnimalsHumansInnate Immunity RecognitionSignal TransductionIFI16 protein, humanNuclear ProteinsPhosphoproteinsRNA-Binding ProteinsZBP1 protein, humanIFI16infectioninflammation regulationinnate immunitynucleic acid sensorPANoptosispyroptosisZBP1

Identifiers

PMID42840615
PMCPMC13639999

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.