Summary of project PR002586
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002586. The data can be accessed directly via it's Project DOI: 10.21228/M8CN8W This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002586 |
| Project DOI: | doi: 10.21228/M8CN8W |
| Project Title: | Taurine transport is a critical modulator of ionic fluxes during NLRP3 inflammasome activation |
| Project Type: | MS exploratory analysis |
| Project Summary: | Metabolic regulation is a key feature of inflammasome activation and effector function. Using metabolomic approaches, we show that downregulation of taurine metabolism is crucial for NLRP3 inflammasome activation. Following NLRP3 activation stimuli, taurine rapidly egresses to the extracellular compartment. Taurine efflux is facilitated primarily by the volume-regulated anion channel (VRAC). Loss of intracellular taurine impairs sodium-potassium ATPase pump activity, promoting ionic dysregulation and disrupting ionic fluxes. Inhibiting VRAC, or supplementation of taurine, restores the ionic balance, abrogates IL-1beta release and reduces cellular cytotoxicity in macrophages. We further demonstrate that the protective effect of taurine is diminished when sodium-potassium ATPase is inhibited, highlighting the pump’s role in taurine-mediated protection. Finally, taurine metabolism is significantly associated with the development of tuberculosis-associated immune reconstitution inflammatory syndrome, a systemic hyperinflammatory condition known to be mediated by inflammasome activation. Altogether, we identified a critical metabolic pathway that modulates inflammasome activation and drives disease pathogenesis. |
| Institute: | Imperial College London |
| Department: | Department of Infectious Disease |
| Laboratory: | Lai's Lab |
| Last Name: | Rossi-Smith |
| First Name: | Peter |
| Address: | Hammersmith Campus, London, London, W12 0NN, United Kingdom |
| Email: | p.rossi@imperial.ac.uk |
| Phone: | 07860694004 |
| Funding Source: | This work was supported by an MRC CDA fellowship (MR/R008922/1) to R.P.J.L. and in part by the NIHR Imperial Biomedical Research Centre and an NIH R01 grant (5R01AI145436) to R.J.W. and R.P.J.L. D.C.T. is supported by a Wellcome-Beit Prize Trust Clinical Research Career Development Fellowship and the Burman Fund from Imperial College London. J.P.G. is supported by MRC research grant (MR/W028867/1). A.E.D. is supported by an MRC CDA fellowship (MR/V009591/1). R.J.W., M.S.S. and J.I.M. are supported by The Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2206), the UK Medical Research Council (CC2206), and the Wellcome Trust (CC2206). T.E. and C.W. acknowledge funding from the BBSRC grant (BB/W002345/1). T.E. acknowledges partial support from UKRI BBSRC grant BB/T007974/1, European Union projects HUMAN (EC101073062) and BiACEM (EC101079370). G.M. was supported by the Wellcome Trust (098316, 214321/Z/18/Z, and 203135/Z/16/Z) and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant no. 64787). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of this report. The opinions, findings and conclusions expressed in this manuscript reflect those of the authors alone. This research was funded, in part, by the Wellcome Trust. For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. |
| Contributors: | Dr. Rachel Lai |
Summary of all studies in project PR002586
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004111 | Metabolic changes in human macrophages following NLRP3 activation | Homo sapiens | Imperial College London | MS* | 2025-08-15 | 1 | 38 | Uploaded data (7.8G)* |
| ST004113 | Metabolic changes in NLRP3 knockout and VRAC knockdown THP-1 derived macrophages following NLRP3 inflammasome activation | Homo sapiens | Imperial College London | MS* | 2025-08-15 | 1 | 45 | Uploaded data (7.5G)* |
| ST004114 | Metabolic changes in murine macrophages following AIM2 and NLRC4 inflammasomes activation | Mus musculus | Imperial College London | MS* | 2025-08-14 | 1 | 20 | Uploaded data (8.9G)* |
| ST004115 | Metabolic changes in murine macrophages following NLRP3 inflammasome activation | Mus musculus | Imperial College London | MS* | 2025-08-17 | 1 | 30 | Uploaded data (8.9G)* |
