Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury

Article Gastroenterology & Hepatology

The Ninj1/Dusp1 Axis Contributes to Liver Ischemia Reperfusion Injury by Regulating Macrophage Activation and Neutrophil Infiltration

Yuanchang Hu et al.

Summary: This study reveals that Ninj1 plays a regulatory role in liver ischemia-reperfusion injury by modulating the inflammatory response of Kupffer cells and reducing neutrophil infiltration.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2023)

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Article Multidisciplinary Sciences

Structural basis of NINJ1-mediated plasma membrane rupture in cell death

Morris Degen et al.

Summary: Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture. The protein ninjurin-1 (NINJ1) mediates the active process of membrane rupture in dying cells. NINJ1 clusters into structurally diverse assemblies in dying cell membranes, particularly large filamentous assemblies with branched morphology. Molecular dynamics simulations show that NINJ1 can stably cap membrane edges. Therefore, NINJ1 is an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death.

NATURE (2023)

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Review Gastroenterology & Hepatology

Liver ischaemia-reperfusion injury: a new understanding of the role of innate immunity

Hirofumi Hirao et al.

Summary: The authors of this Review examine the roles of macrophages, platelets, and neutrophils in liver ischaemia-reperfusion injury (LIRI), discussing potential therapeutic strategies for treating LIRI in transplant recipients. They highlight the unanswered questions in understanding the mechanisms underlying the responses of these cells in the acute phase of LIRI, and discuss prospects for innovative therapeutic regimens against LIRI in transplant recipients.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2022)

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Review Immunology

TNF in the liver: targeting a central player in inflammation

Gisa Tiegs et al.

Summary: Tumour necrosis factor-alpha (TNF) is a multifunctional cytokine that plays important roles in immunopathogenesis and liver functions. Targeting TNF signalling through anti-TNF therapies could be a potential treatment for TNF-related diseases.

SEMINARS IN IMMUNOPATHOLOGY (2022)

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Article Immunology

Role of NINJ1 in Gout Flare and Potential as a Drug Target

Hongliang Zhang et al.

Journal of Inflammation Research (2022)

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Article Multidisciplinary Sciences

NINJ1 mediates plasma membrane rupture during lytic cell death

Nobuhiko Kayagaki et al.

Summary: Plasma membrane rupture is a cataclysmic event in lytic cell death, releasing damage-associated molecular patterns to propagate the inflammatory response. NINJ1 protein plays an essential role in inducing PMR, with Ninj1-deficient macrophages showing impaired release of intracellular proteins and distinctive ballooned morphology. This study overturns the long-held belief that cell death-related PMR is a passive event, highlighting the active role of NINJ1 in mediating PMR.

NATURE (2021)

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Article Genetics & Heredity

Genetics of 35 blood and urine biomarkers in the UK Biobank

Nasa Sinnott-Armstrong et al.

Summary: The study evaluated the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank, identifying 1,857 loci associated with at least one trait. Through Mendelian randomization analysis, 51 causal relationships were discovered, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, by developing polygenic risk scores and building 'multi-PRS' models, genetic risk stratification for common diseases was improved.

NATURE GENETICS (2021)

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Article Microbiology

Genetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection

Elisabet Bjanes et al.

Summary: Programmed cell death is crucial for tissue homeostasis and host defense, with pyroptosis being an inflammatory form involving cell lysis and release of cytokines. Genetic targeting of Card19 impacts adjacent gene Ninj1, regulating processes of cell lysis downstream of gasdermin cleavage and influencing susceptibility to bacterial infections.

PLOS PATHOGENS (2021)

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Article Multidisciplinary Sciences

Gasdermin D pore structure reveals preferential release of mature interleukin-1

Shiyu Xia et al.

Summary: Inflammasomes activate caspase-1 to cleave GSDMD and generate mature cytokines like IL-1 beta and IL-18, which are released through pores formed by GSDMD. The GSDMD pore mediates IL-1 release by electrostatic filtering, favoring the passage of mature cytokines over their precursors.

NATURE (2021)

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Article Biochemistry & Molecular Biology