Evidence map›Paper›PMID 42312921›Full record

ArticleInvestigative ophthalmology & visual science2026

Time-Course Transcriptomic Analysis Reveals PANoptosis-CCL2 Axis in Herpes Simplex Keratitis.

Changyu Wu, Junwen Ouyang, Yaoyao Liu, Boxiao Zhao, Qian Wang, Junpeng Liu, Jiaxuan Jiang, Kai Hu

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 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

8 authors.

Changyu WuDepartment of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Junwen OuyangDepartment of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Yaoyao LiuDepartment of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Boxiao ZhaoDepartment of Ophthalmology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
Qian WangDepartment of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Junpeng LiuDepartment of Ophthalmology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
Jiaxuan JiangDepartment of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Kai HuDepartment of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: This study aimed to characterize the temporal dynamics of corneal immune responses and programmed cell death (PCD) following herpes simplex virus type 1 (HSV-1) infection, and investigate the role of PANoptosis in shaping the immune responses during herpes simplex keratitis (HSK). Methods: A murine HSK model was established through HSV-1 infection, and time-course RNA sequencing was performed on murine corneas at 0, 1, 3, 7, and 14 days post-infection. Phenotypic and mechanistic analyses were conducted using quantitative real-time PCR, western blotting, immunofluorescence staining, flow cytometry, and co-culture experiments. PCD pathways were assessed using antagonists targeting PANoptosis, an integrated form of cell death encompassing key features of apoptosis, pyroptosis, and necroptosis. Results: RNA sequencing revealed sequential immune response phases in the cornea following HSV-1 infection: homeostasis disruption and transcriptional activation (0-3 days), immune amplification (3-7 days), and tissue reorganization (7-14 days). The immune amplification phase was strongly associated with the activation of three distinct PCD pathways: apoptosis, pyroptosis, and necroptosis, culminating in PANoptosis. PANoptosis was confirmed as a central mechanism in HSK pathogenesis, with Z-DNA-binding protein 1 (ZBP1) serving as a key driver of PANoptosome formation. Furthermore, PANoptosis in human corneal epithelial cells (HCECs) was shown to promote the release of C-C motif chemokine ligand 2 (CCL2), enhancing macrophage major histocompatibility complex class II (MHC-II) and interferon β (IFN-β) expression and migration. The PANoptosis-CCL2/C-C motif chemokine receptor 2 (CCR2) axis was significantly upregulated in infected corneas and could be suppressed by a PANoptosis inhibitor or the CCL2 antagonist Bindarit. Conclusions: This study demonstrated the temporal coordination between immune activation and PANoptosis in HSK, highlighting PANoptosis as a crucial mechanism in amplifying antiviral immune responses. The ZBP1-PANoptosome-mediated PANoptosis-CCL2/CCR2 axis represents a potential therapeutic target for modulating the immune responses in HSK.

Indexed as

Chemokine CCL2Eye Infections, ViralKeratitis, HerpeticAnimalsApoptosisBlotting, WesternCorneaDisease Models, AnimalFemaleFlow CytometryGene Expression ProfilingHerpesvirus 1, HumanMiceMice, Inbred C57BLReal-Time Polymerase Chain ReactionCcl2 protein, mouseChemokine CCL2

Identifiers

PMID42312921
PMCPMC13284957

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.