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Cited by 48Inflammasome and immune disordersLiver Diseases and ImmunityImmune Response and Inflammation

NLRP3 inflammasome activation mechanism and its role in autoimmune liver disease

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Guan, Yanling, Gu, Yiyue, Li, Hao, Liang, Bo, Han, Chenchen, Zhang, Yu, Liu, Qian, Wei, Wei +1 more·2022·Acta Biochimica et Biophysica Sinica
DOI 10.3724/abbs.2022137PMC PMC9828325
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Abstract

The NLRP3 inflammasome is a multiprotein binding compound comprising NLRP3, connector protein ASC, and effector protein pro-caspase-1. When the NLRP3 inflammasome senses a danger signal from the host or pathogen, activated caspase-1 cleaves the precursors of interleukin (IL)-1β and IL-18 into mature proinflammatory cytokines, simultaneously causing lysis via the pore-forming protein gasdermin D. This induction of cell inflammatory pyroptosis suggests that it is a key process in the innate immune response to pathogens or cellular stress. Recent studies have shown that NLRP3 inflammasome also plays an important role in regulating autoimmune liver diseases, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosclerotic cholangitis. In this review, we summarize the structure, activation and modulation of the NLRP3 inflammasome, highlight the progress in research on the role of NLRP3 inflammasome in the occurrence and development of autoimmune liver diseases, and discuss potential strategies for targeting the NLRP3 inflammasome in the treatment of autoimmune liver diseases.

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  • TNF-α and IL-1β activate NF-κB in HSCs, inducing pro-fibrotic gene expression and inhibiting HSC apoptosis.

    “Pro-inflammatory cytokines TNF-α and IL-1β (secreted by M1 macrophages) activate NF-κB within HSCs, inducing pro-fibrotic gene expression and inhibiting HSC apoptosis.”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [34]

    The Autoimmune hepatitis section (page unavailable) says activated macrophages release IL-1 and TNF-α, and that IL-1β is abundant in the liver microenvironment. It does not identify those macrophages as M1 or say that the cytokines activate NF-κB in HSCs, induce pro-fibrotic genes, or inhibit HSC apoptosis. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • TGF-β1 binds TβRII on HSCs, phosphorylates Smad2/3; the complex translocates to the nucleus, activating α-SMA, collagen I/III, and TIMP-1 while suppressing MMPs.

    “TGF-β1 (released by Kupffer cells, platelets, and injured hepatocytes) binds to TβRII receptors on HSCs, leading to phosphorylation of Smad2/3. The phospho-Smad2/3-Smad4 complex translocates to the nucleus, activating genes encoding α-smooth muscle actin (α-SMA), collagen I and III, and tissue inhibitor of metalloproteinase-1 (TIMP-1) while suppressing matrix metalloproteinases (MMPs).”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [34]

    The Primary biliary cholangitis section mentions a mouse model with a dominant-negative TGF-β receptor II, but discusses Gal3-driven NLRP3 activation rather than TGF-β1 signaling in hepatic stellate cells. Searches for Smad2/3, stellate cells, collagen, TIMP-1, and MMPs found no passage describing the attributed pathway. Page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Chemokines CCL2 and CXCL8 recruit monocytes, perpetuating the inflammatory response and fibrosis.

    “Chemokines such as CCL2 and CXCL8 recruit monocytes, perpetuating the inflammatory response and fibrosis [33, 34].”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [34]

    The Autoimmune hepatitis section discusses inflammatory cytokines, and the Primary biliary cholangitis section mentions monocytes, but neither describes chemokine-driven monocyte recruitment or its contribution to fibrosis. Searches for CCL2, CXCL8, and monocyte recruitment found no passage supporting the attributed mechanism. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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References 124 · Cited by 48

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Authors
Guan, Y., Gu, Y., Li, H., Liang, B., Han, C., Zhang, Y., Liu, Q., Wei, W., & Ma, Y.
Affiliations
  • Anhui Medical University (CN)
  • Xuzhou No.1 People's Hospital (CN)
Corresponding author
  • Wei, Wei
  • Ma, Yang
ORCID
Venue
Acta Biochimica et Biophysica Sinica
Publisher
China Science Publishing & Media Ltd.
Published
2022-09-23
Volume
54
Issue
11
Pages
1577-1586
ISSN
1672-9145 (ISSN-L)
DOI
10.3724/abbs.2022137
PMC
PMC9828325
OpenAlex
W4296119962
Cited by
48
References
124
Citations by year
2026: 15 · 2025: 12 · 2024: 10 · 2023: 11
FWCI
0.86
Type
journal article
Language
en
Open access
Locations
  • Acta Biochimica et Biophysica Sinica (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
NLRP3 inflammasome, inflammasome activation, caspase-1, IL-1β, IL-18, gasdermin D, pyroptosis, autoimmune liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, innate immunity, inflammasome-targeted therapy
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Humans, Immunity, Innate, Liver Diseases, Caspase 1, Interleukin-1beta, Inflammasomes

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