Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells. In human liver transplant patients undergoing progressive immunosuppressive drug withdrawal, we found that patients experiencing acute rejection had higher levels of the P2X7 receptor in circulating inflammatory monocytes compared to tolerant patients. These data suggest that the pharmacological inhibition of the P2X7 receptor or the NLRP3 inflammasome will aid in inducing transplant tolerance without complete immunoparalysis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746605 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2017.11.079 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Macrophage NLRP3-dependent IL-1β production contributes to aortic fibrosis in heart failure with preserved ejection fraction.
Acta Biochim Biophys Sin (Shanghai)
December 2024
Fibrosis is the main pathological feature of aortic stiffness, which is a common extracardiac comorbidity of heart failure with preserved ejection fraction (HFpEF) and a contributor to left ventricular (LV) diastolic dysfunction. Systemic low-grade inflammation plays a crucial role in the pathogenesis of HFpEF and the development of vascular fibrosis. In this study, we investigate the inflammatory mechanism of aortic fibrosis in HFpEF using a novel mouse model.
View Article and Find Full Text PDFFibroblast Growth Factor 21 Confers Protection Against Asthma Through Inhibition of NLRP3 Inflammasome Activation.
Inflammation
December 2024
Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, No.127 Changle West Road, Xi'an, 710032, China.
Fibroblast growth factor 21 (FGF21) modulates the inflammatory response in a range of pathological conditions. However, whether FGF21 modulates asthma remains unexplored. This study sought to investigate its function in asthma using an ovalbumin (OVA)-induced mouse model.
View Article and Find Full Text PDFGalvanic current has been emerging as a novel therapy to regenerate chronic tissue lesions, including musculoskeletal and dermatological lesions. Recently, the NLRP3 inflammasome and IL-1β release have been identified as a signaling pathway triggered upon galvanic current application. However, the parameters for the clinical application of galvanic current remain subjective to the experience of the facultative in charge.
View Article and Find Full Text PDFForsythoside B Ameliorates Neuroinflammation via Inhibiting NLRP3 Inflammasome of Glial Cells in Experimental Autoimmune Encephalomyelitis Mice.
Brain Res Bull
December 2024
Department of Neurology, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, China. Electronic address:
Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and anti-inflammatory properties.
View Article and Find Full Text PDFSodium butyrate prevents lipopolysaccharide induced inflammation and restores the expression of tight junction protein in human epithelial Caco-2 cells.
Cell Immunol
December 2024
Defence Institute of Physiology and Allied Sciences, Delhi 110054, India. Electronic address:
The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as a metabolite in the gut, has emerged as a promising therapeutic agent due to its ability to act as an immunomodulatory agent and restore intestinal barrier integrity. This study aimed to explore the mechanism by which sodium butyrate exhibits anti inflammatory effect on intestinal epithelial cells.
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!