{
  "id": 17729166,
  "title": "A network of bZIP transcription factors and inhibitors enforces differentially proliferative and cytotoxic states in T cells",
  "url": "https://urgent.news/2026/11/01/a-network-of-bzip-transcription-factors-and-inhibitors-enforces",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-01T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762687v1?rss=1"
  },
  "original_language": "en",
  "account": "A network of bZIP transcription factors and inhibitors influence T-cell proliferation and cytotoxicity, according to a recent study. The research reveals that varying bZIP TF activity through overexpression or inhibition impacts CAR T-cell expansion under conditions of exhaustion. This method employs inhibitors targeting pro-exhaustion TFs, like CREM and NFIL3, providing insight into the roles of full-length TFs. BATF2 emerges as an underappreciated bZIP TF with anti-exhaustion potential. A series of tests on various bZIP TFs and inhibitors uncovers distinct effects on proliferation, persistence, and cytotoxicity. Pairings of pro-cytotoxic JUN, pro-proliferative BATF2, and the novel inhibitor AEL-CREM of pro-dysfunction CREM yield combinations that enhance either cytotoxicity or proliferation, indicating relationships between BATF2, JUN-, and CREB1-family bZIPs. Further investigation reveals functional overlap in the inhibition of pro-dysfunction CREB1-family activity by BATF2 and AEL-CREM, possibly through unexpected interactions of CREB1-family members with overexpressed BATF2. BATF2's influence extends to early promotion of pro-proliferation AP-1 activity and later interactions with BACH2, contributing to persistence. These discoveries are corroborated in murine chronic viral infection and syngeneic tumor models, where BATF2 or AEL-CREM overexpression demonstrates pro-proliferative and anti-exhaustion effects. The findings shed light on new connections and functional roles of bZIP family perturbations, offering potential strategies to modulate T-cell states.",
  "summary": "The bZIP family of transcription factors (TFs) plays a central role in regulating T-cell exhaustion. Their complex dimeric interactions obscure the roles of individual members, which genetic knockout or overexpression alone poorly resolve. Here, we use overexpression of full-length bZIP family TFs alongside genetically encoded, protein-based inhibitors to probe the effect of increased or…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}