ArticleJCI insight2024
Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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
10 citing papers in PubMed, 12 citations in OpenAlex.
- Single-cell multi-omic profiling of heterogeneous PROCRiScience · 2026Article
- Restoration of Keratinocyte Homeostasis Drives Resolution of Skin Inflammation.bioRxiv : the preprint server for biology · 2026Article
- The RNA binding protein Arid5a is an activator of TNF signaling in rheumatoid arthritis.JCI insight · 2026Article
- G-CSF Mediates Increased Renal Neutrophils and Kidney Damage in a Psoriasis Mouse Model.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Bioinformatics and experimental approach identify DNMT3A as a diagnostic marker associated with regulated cell death patterns in psoriasis.Journal, genetic engineering & biotechnology · 2025Article
- Multiple cell types guided by neurocytes orchestrate horn bud initiation in dairy goats.Genetics, selection, evolution : GSE · 2025Article
- An unbiased tissue transcriptome analysis identifies potential markers for skin phenotypes and therapeutic responses in atopic dermatitis.Nature communications · 2025Article
- Exploring the association between 91 circulating inflammatory proteins and the risk of carcinoid syndrome: a Mendelian randomization analysis.Discover oncology · 2025Article
- Skeletal muscle vulnerability in a child with Pitt-Hopkins syndrome.Skeletal muscle · 2024Article
- Identification of crosstalk genes and immune characteristics between Alzheimer's disease and atherosclerosis.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
IL-17C is an epithelial cell-derived proinflammatory cytokine whose transcriptional regulation remains unclear. Analysis of the IL17C promoter region identified TCF4 as putative regulator, and siRNA knockdown of TCF4 in human keratinocytes (KCs) increased IL17C. IL-17C stimulation of KCs (along with IL-17A and TNF-α stimulation) decreased TCF4 and increased NFKBIZ and ZC3H12A expression in an IL-17RA/RE-dependent manner, thus creating a feedback loop. ZC3H12A (MCPIP1/Regnase-1), a transcriptional immune-response regulator, also increased following TCF4 siRNA knockdown, and siRNA knockdown of ZC3H12A decreased NFKBIZ, IL1B, IL36G, CCL20, and CXCL1, revealing a proinflammatory role for ZC3H12A. Examination of lesional skin from the KC-Tie2 inflammatory dermatitis mouse model identified decreases in TCF4 protein concomitant with increases in IL-17C and Zc3h12a that reversed following the genetic elimination of Il17c, Il17ra, and Il17re and improvement in the skin phenotype. Conversely, interference with Tcf4 in KC-Tie2 mouse skin increased Il17c and exacerbated the inflammatory skin phenotype. Together, these findings identify a role for TCF4 in the negative regulation of IL-17C, which, alone and with TNF-α and IL-17A, feed back to decrease TCF4 in an IL-17RA/RE-dependent manner. This loop is further amplified by IL-17C-TCF4 autocrine regulation of ZC3H12A and IL-17C regulation of NFKBIZ to promote self-sustaining skin inflammation.
Indexed as
Identifiers
What Socratic 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 Socratic graph.