Synergistic interaction between the macrophage polarizing signals IL-4 and IFNγ is controlled by the STAT6/STAT1/IRF1 axis

Clicks: 21
ID: 326551
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #175 of 1,224 articles by views in Nucleic Acids Research

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 1,224 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
IFNγ and IL-4, the canonical Th1 and Th2 cytokines, typically induce opposing macrophage polarization. Beyond their frequent coexistence and mutual antagonism in pathological settings, a synergistic crosstalk may also exist and remains to be defined. Through integrated transcriptomic, epigenomic, and CRISPR-based analyses, we identify that co-exposure to IL-4 and IFNγ results in an intermediate macrophage polarization state in murine macrophages, associated with a cohort of synergistically activated genes. We show that this synergistic activation is mediated by co-binding of STAT6 and STAT1 at regulatory regions marked with pronounced H3K27Ac accumulation and is dependent on the BRD4 cofactor. Deletion of either STAT factor or disruption of their binding motifs abolishes the synergistic transcriptional response. Our data support a model in which chromatin openness induced by one cytokine facilitates binding of the opposing cytokine-activated STAT transcription factor (TF), contributing to synergistic gene activation. We further show that IRF1, an IFNγ-induced TF whose expression persists in the presence of IL-4, is indispensable for a substantial subset of this program. Importantly, single-cell RNA sequencing of the PyMT murine breast cancer model reveals an in vivo tumor-associated macrophage subset showing STAT1 and STAT6 activation and is enriched for the synergistic gene signature.
Reference Key
openalex_W7204233473 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Zsofia Varga, Anna Poscher, Eszter Anna Váradi, Gyöngyi Cinege, Antal Izsán, Edina Erdős, Bernadett Benyhe-Kis, Anna Zsuzsanna Tihanyi, Petros Tzerpos, Krisztian Bene, László Halász, Nikolett Gémes, Patrícia Neuperger, Márta Tóth, Ede Migh, Szilárd Póliska, Gábor J Szebeni, Jolán E. Walter, Bence Dániel, Bálint Csörgő, László Nagy, Zsolt Czimmerer
Journal Nucleic Acids Research
Year 2026
DOI
10.1093/nar/gkag825
URL
https://doi.org/10.1093/nar/gkag825
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.