The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4(+) T cells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (T(H)1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to "innate immune cells" but is an integral component of normal adaptive T(H)1 responses.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015487 | PMC |
| http://dx.doi.org/10.1126/science.aad1210 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dihydrotanshinone I Attenuates Diet-Induced Nonalcoholic Fatty Liver Disease via Up-Regulation of IRG1.
Phytother Res
January 2025
Department of Endocrinology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, but effective therapeutic drugs are still lacking. Dihydrotanshinone I (DHTS), a natural product isolated from Salvia miltiorrhiza, has been shown to have ameliorative effects on NAFLD. The aim of this study was to investigate the hepatoprotective effect of DHTS on NAFLD and its mechanism.
View Article and Find Full Text PDFRole of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.
J Biochem Mol Toxicol
February 2025
Department of Histology and Embryology, Faculty of Basic Medical Sciences, Hubei University of Medicine, Shiyan, People's Republic of China.
The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions.
View Article and Find Full Text PDFMethyl Canthin-6-one-2-carboxylate Inhibits the Activation of the NLRP3 Inflammasome in Synovial Macrophages by Upregulating Nrf2 Expression.
Curr Issues Mol Biol
January 2025
Graduate School, Dalian Medical University, Dalian 116044, China.
Rheumatoid arthritis (RA) is an autoimmune disorder that leads to severe cartilage deterioration and synovial impairment in the joints. Previous studies have indicated that the aberrant activation of the NLRP3 inflammasome in synovial macrophages plays a significant role in the pathogenesis of RA and has been regarded as a therapeutic target for the disease. In this study, we synthesized a novel canthin-6-one alkaloid, namely methyl canthin-6-one-2-carboxylate (Cant), and assessed its effects on NLRP3 inflammasome activation in macrophages.
View Article and Find Full Text PDFMechanisms and Emerging Regulators of Neuroinflammation: Exploring New Therapeutic Strategies for Neurological Disorders.
Curr Issues Mol Biol
December 2024
Immunology Research Lab & BK21-Four Educational Research Group for Age-Associated Disorder Control Technology, Department of Biological Science, Chosun University, Gwangju 61452, Republic of Korea.
Neuroinflammation is a complex and dynamic response of the central nervous system (CNS) to injury, infection, and disease. While acute neuroinflammation plays a protective role by facilitating pathogen clearance and tissue repair, chronic and dysregulated inflammation contributes significantly to the progression of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. This review explores the cellular and molecular mechanisms underlying neuroinflammation, focusing on the roles of microglia, astrocytes, and peripheral immune cells.
View Article and Find Full Text PDFmiR-223 and Chromogranin A Affect Inflammatory Immune Cell Activation in Liver Metastasis of Neuroendocrine Neoplasms.
Cells
January 2025
Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, 13353 Berlin, Germany.
Neuroendocrine neoplasms (NENs) are a diverse group originating from endocrine cells/their precursors in pancreas, small intestine, or lung. The key serum marker is chromogranin A (CgA). While commonly elevated in patients with NEN, its prognostic value is still under discussion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!