Inflammasomes in Intestinal Inflammation: Guardians of Mucosal Homeostasis, Amplifiers of Disease, and Targets for Intervention
Abstract
The intestinal mucosa is continuously exposed to dietary antigens, commensal microorganisms, and enteric pathogens, thereby depending on innate immune pathways that detect danger without compromising tissue tolerance. Inflammasomes are cytosolic signaling platforms linking microbial- or stress-sensing to caspase activation, interleukin-1 family cytokine maturation, and gasdermin-dependent membrane responses. In the gut, these pathways support epithelial restitution, mucus and antimicrobial secretion, epithelial cell expulsion, and pathogen containment. Nonetheless, these pathways can drive chronic inflammation through sustained interleukin (IL)-1β production, pyroptosis, neutrophil recruitment, and pathogenic adaptive immunity reinforcement. This review synthesizes the current view of how canonical and noncanonical inflammasomes operate in intestinal epithelial and immune cells, with an emphasis on NLR family pyrin domain-containing (NLRP) 3, NLRP6, NLR family CARD domain-containing (NLRC) 4, Absent in melanoma (AIM) 2, and pyrin. We discuss how cell-intrinsic programs intersect with the microbiota, why protective and pathogenic findings coexist, and how human genetics is beginning to define inflammasome-rich subsets of intestinal diseases. Recent retrospective cohort data sharpen the clinical relevance of pyrin biology: among 396 Japanese patients with inflammatory bowel disease unclassified, 60.1% carried Mediterranean fever (MEFV) variants, and colchicine response among evaluable mutation-positive cases reached 84.6%, thus supporting a distinct colchicine-responsive, IL-1β-skewed enterocolitis subset. Finally, biomarkers and therapeutic opportunities are outlined, and unresolved questions most likely to shape precision-medicine approaches for inflammatory bowel disease and related intestinal autoinflammatory syndromes are identified.
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BibTeX
@article{nakase2026inflammasomes,
title = {{Inflammasomes in Intestinal Inflammation: Guardians of Mucosal Homeostasis, Amplifiers of Disease, and Targets for Intervention}},
author = {Hiroshi Nakase and Yuta Shimomori and Hiroki Kurumi},
journal = {Internal Medicine},
year = {2026},
month = jul,
doi = {10.2169/internalmedicine.7768-26},
url = {https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7768-26/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Inflammasomes in Intestinal Inflammation: Guardians of Mucosal Homeostasis, Amplifiers of Disease, and Targets for Intervention
AU - Hiroshi Nakase
AU - Yuta Shimomori
AU - Hiroki Kurumi
PY - 2026
DA - 2026/07/04
JO - Internal Medicine
DO - 10.2169/internalmedicine.7768-26
UR - https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7768-26/_article
AB - The intestinal mucosa is continuously exposed to dietary antigens, commensal microorganisms, and enteric pathogens, thereby depending on innate immune pathways that detect danger without compromising tissue tolerance. Inflammasomes are cytosolic signaling platforms linking microbial- or stress-sensing to caspase activation, interleukin-1 family cytokine maturation, and gasdermin-dependent membrane responses. In the gut, these pathways support epithelial restitution, mucus and antimicrobial secretion, epithelial cell expulsion, and pathogen containment. Nonetheless, these pathways can drive chronic inflammation through sustained interleukin (IL)-1β production, pyroptosis, neutrophil recruitment, and pathogenic adaptive immunity reinforcement. This review synthesizes the current view of how canonical and noncanonical inflammasomes operate in intestinal epithelial and immune cells, with an emphasis on NLR family pyrin domain-containing (NLRP) 3, NLRP6, NLR family CARD domain-containing (NLRC) 4, Absent in melanoma (AIM) 2, and pyrin. We discuss how cell-intrinsic programs intersect with the microbiota, why protective and pathogenic findings coexist, and how human genetics is beginning to define inflammasome-rich subsets of intestinal diseases. Recent retrospective cohort data sharpen the clinical relevance of pyrin biology: among 396 Japanese patients with inflammatory bowel disease unclassified, 60.1% carried Mediterranean fever (MEFV) variants, and colchicine response among evaluable mutation-positive cases reached 84.6%, thus supporting a distinct colchicine-responsive, IL-1β-skewed enterocolitis subset. Finally, biomarkers and therapeutic opportunities are outlined, and unresolved questions most likely to shape precision-medicine approaches for inflammatory bowel disease and related intestinal autoinflammatory syndromes are identified.
SN - 1349-7235
SN - 0918-2918
ER -