ArticleFrontiers in immunology2026
Post-transcriptional regulation via alternative polyadenylation and piRNA shapes macrophage responses in psoriasis.
Article 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.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Post-transcriptional regulatory mechanisms underlying autoimmune diseases remain poorly understood. Here, we employed integrated multi-omics approaches to systematically dissect the role of alternative polyadenylation (APA) and piRNA-mediated regulation in psoriasis pathogenesis. Methods: We performed transcriptome-wide association studies (TWAS) combined with Mendelian randomization to identify causal susceptibility genes. Long-read sequencing was used to characterize APA landscapes in 15 healthy controls and 10 psoriasis patients. Single-cell RNA sequencing was performed on lesional tissues from 4 patients to define cell-specific expression patterns. Small RNA sequencing was conducted to profile piRNA regulation in LPS + IFN-γ-polarized THP-1 macrophages following TDRKH knockdown. Results: Integrating multi-tissue genetic validations across GTEx, eQTLGen, and FinnGen datasets, we identified TDRKH as a robust psoriasis susceptibility gene (PPH4 > 0.92). TDRKH exhibited significant APA alterations in psoriatic PBMCs, with preferential usage of the distal polyadenylation site leading to 3'UTR lengthening (PDI = -0.574). Reporter gene assays confirmed that the long 3'UTR isoform conferred approximately 3-fold greater mRNA stability (t½ = 6.9 h vs. 2.3 h). Single-cell RNA sequencing of psoriatic skin (4 patients, 17,734 cells) identified 17 cell types and 10 macrophage/myeloid subpopulations using marker gene-based annotation with TDRKH excluded from feature selection. TDRKH expression was highest in IL-23-producing macrophages (IL23A+IL1B+), which were selectively enriched in lesional tissue. TDRKH knockdown in LPS + IFN-γ-polarized THP-1 macrophages altered piRNA expression profiles, reduced pro-inflammatory surface markers (CD80, CD86, HLA-DR), and attenuated IL6 and IL1B expression, supporting a functional role of the TDRKH-piRNA axis in macrophage inflammatory activation. Conclusions: Our findings reveal a previously unrecognized post-transcriptional regulatory network involving APA and piRNA that governs macrophage-driven inflammation. The discovery of the TDRKH-piRNA axis provides novel mechanistic insights into psoriasis and establishes a potential therapeutic target.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.