A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses DOI Creative Commons
Masahiro Nagata, Yasmin Carvalho Schäfer, Laurens Wachsmuth

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Abstract Z-DNA-binding protein 1 (ZBP1) is an interferon-inducible sensor of Z-DNA and Z-RNA, which has emerged as a critical regulator cell death inflammation. ZBP1 binds Z-RNA via its Zα domains, signals by engaging RIPK3 RIPK1 RIP homotypic interaction motifs (RHIMs). Here, we show that mice express alternatively-spliced shorter isoform (ZBP1-S), harbours the domains but lacks RHIMs, acts endogenous inhibitor full-length (ZBP1-L). Mice cells expressing only ZBP1-S are resistant to ZBP1-mediated In contrast, lacking increased ZBP1-L-induced compared both isoforms. Moreover, loss short accelerates exacerbates skin inflammation induced necroptosis RIPK1-deficient keratinocytes, revealing important physiological role ZBP1-S. Mechanistically, suppresses ZBP1-L-mediated binding Z-nucleic acids domains. Therefore, competes with ZBP1-L for acid ligands fine-tune

Language: Английский

Z‐Nucleic Acid Sensing and Activation of ZBP1 in Cellular Physiology and Disease Pathogenesis DOI Open Access

Sanchita Mishra,

Ayushi Amin Dey,

Sannula Kesavardhana

et al.

Immunological Reviews, Journal Year: 2025, Volume and Issue: 329(1)

Published: Jan. 1, 2025

ABSTRACT Z‐nucleic acid binding protein 1 (ZBP1) is an innate immune sensor recognizing nucleic acids in Z‐conformation. Upon sensing, ZBP1 triggers activation, inflammation, and programmed cell death during viral infections, mice development, inflammation‐associated diseases. The Zα domains of sense promote RIP‐homotypic interaction motif (RHIM)‐dependent signaling complex assembly to mount inflammation. studies on spurred understanding the role Z‐form RNA DNA cellular physiological functions. In particular, short genomic segments, endogenous retroviral elements, 3′UTR regions are likely sources Z‐RNAs that orchestrate Recent seminal identify intriguing association with adenosine deaminase acting RNA‐1 (ADAR1), cyclic GMP‐AMP synthase (cGAS) regulating aberrant chronic cancer. Thus, attractive target aid development specific therapeutic regimes for disease biology. Here, we discuss Z‐RNA activation death, Also, how coordinates intracellular perturbations homeostasis, formation regulate diseases

Language: Английский

Citations

2
ZBP1 senses splicing aberration through Z-RNA to promote cell death DOI

Zhang-Hua Yang,

Puqi Wu,

Bo-Xin Zhang

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

1
Comparison of naturalization mouse model setups uncover distinct effects on intestinal mucosa depending on microbial experience DOI Creative Commons
Henriette Arnesen,

Signe Birkeland,

Harriet Stendahl

et al.

Discovery Immunology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 1, 2025

Abstract Introduction Concerns regarding the translational value of preclinical mouse models have been addressed by introducing various approaches ‘naturalizing’ research mice, which provide them with more diverse microbiomes and physiological immune responses. We previously shown that ‘feralized’ is, inbred laboratory mice raised in a farmyard-like, microbe-rich environment exhibit shifted gut microbiota, matured immunophenotype, reduced severity colorectal cancer. Similar studies occasionally involve co-housing wild or pet-store-raised as microbial donors integrating species-specific commensals pathogens. To what extent these different practices exposure are crucial for resulting phenotype remains unclear. Methods Here, we present first side-by-side comparison methods to naturalize mice: wild-caught house feralization farmyard-like habitat only, combination two, conventional clean reference. Results Independent method, naturalized colon-mucosa was colonized several Helicobacter species, colonic intestinal epithelial cells displayed elevated expression genes encoding antimicrobial peptides, mucus components, reactive-oxygen-species-producing enzymes. They further showed significantly increased resident memory T lamina propria effector mesenteric lymph nodes. The most pronounced changes parameters occurred co-housed while feralized phenotypes were intermediate between mice. Conclusion These findings enhance our understanding naturalization model setups effects on barrier system, thereby aiding future decisions utilization models.

Language: Английский

Citations

0
Licochalcone B attenuates pulmonary fibrosis via inhibiting ZBP1-dependent PANoptosis DOI

Hong Ren,

Caiping Zhao, Linuo Zhou

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119940 - 119940

Published: May 1, 2025

Language: Английский

Citations

0
A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses DOI Creative Commons
Masahiro Nagata, Yasmin Carvalho Schäfer, Laurens Wachsmuth

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Abstract Z-DNA-binding protein 1 (ZBP1) is an interferon-inducible sensor of Z-DNA and Z-RNA, which has emerged as a critical regulator cell death inflammation. ZBP1 binds Z-RNA via its Zα domains, signals by engaging RIPK3 RIPK1 RIP homotypic interaction motifs (RHIMs). Here, we show that mice express alternatively-spliced shorter isoform (ZBP1-S), harbours the domains but lacks RHIMs, acts endogenous inhibitor full-length (ZBP1-L). Mice cells expressing only ZBP1-S are resistant to ZBP1-mediated In contrast, lacking increased ZBP1-L-induced compared both isoforms. Moreover, loss short accelerates exacerbates skin inflammation induced necroptosis RIPK1-deficient keratinocytes, revealing important physiological role ZBP1-S. Mechanistically, suppresses ZBP1-L-mediated binding Z-nucleic acids domains. Therefore, competes with ZBP1-L for acid ligands fine-tune

Language: Английский

Citations

2