Genomes and Genes
Luke A O'Neill
Affiliation: Trinity College
- Mills E, Kelly B, Logan A, Costa A, Varma M, Bryant C, et al. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell. 2016;167:457-470.e13 pubmed publisher..The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state. ..
- O Neill L, Hardie D. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature. 2013;493:346-55 pubmed publisher..Altered metabolism may thus participate in the signal-directed programs that promote or inhibit inflammation. ..
- O Neill L. The Hunger Games: Salmonella, Anorexia, and NLRP3. Cell Metab. 2017;25:225-226 pubmed publisher..The mechanism involves inhibition of the NLRP3 inflammasome limiting vagal nerve stimulation by IL-1β, which in turn promotes appetite. A possible new therapeutic approach for treating anorexia in multiple diseases is proposed. ..
- O Neill L, Golenbock D, Bowie A. The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol. 2013;13:453-60 pubmed publisher..TLRs have a central role in immunity - in this Timeline article, we describe the landmark findings that gave rise to this important field of research. ..
- Mills E, O Neill L. Succinate: a metabolic signal in inflammation. Trends Cell Biol. 2014;24:313-20 pubmed publisher..We review the new roles of succinate and draw parallels to other metabolites such as NAD(+) and citrate whose roles have expanded beyond metabolism and into signaling. ..
- O Neill L. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev. 2008;226:10-8 pubmed publisher..This area has therefore proved very fruitful in terms of improving our knowledge of the molecular basis for innate immunity and inflammation, and we can anticipate further discoveries in the coming years. ..
- ZasÅ‚ona Z, Case S, Early J, Lalor S, McLoughlin R, Curtis A, et al. The circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma. Am J Physiol Lung Cell Mol Physiol. 2017;312:L855-L860 pubmed publisher..This suggests that Bmal1 is a potent negative regulator in myeloid cells in the context of allergic asthma. Our findings might explain the increase in asthma incidents during the night, when BMAL1 expression is low. ..
- O Neill L, Sheedy F, McCoy C. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol. 2011;11:163-75 pubmed publisher..miRNAs are also proving to be an important link between the innate and adaptive immune systems, and their dysregulation might have a role in the pathogenesis of inflammatory diseases. ..
- Zasłona Z, Palsson McDermott E, Menon D, Haneklaus M, Flis E, Prendeville H, et al. The Induction of Pro-IL-1? by Lipopolysaccharide Requires Endogenous Prostaglandin E2 Production. J Immunol. 2017;198:3558-3564 pubmed publisher..Furthermore, fever might therefore occur in the absence of a septic shock response because of the inhibiting effect of PGE2 on TNF-? production. ..
- Haneklaus M, O Neil J, Clark A, Masters S, O Neill L. The RNA-binding protein Tristetraprolin (TTP) is a critical negative regulator of the NLRP3 inflammasome. J Biol Chem. 2017;292:6869-6881 pubmed publisher..Because TTP also represses IL-1Î² expression, it is a dual inhibitor of the IL-1Î² system, regulating expression of the cytokine and the upstream controller NLRP3. ..
- Greenhill C, Jones G, Nowell M, Newton Z, Harvey A, Moideen A, et al. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Res Ther. 2014;16:419 pubmed publisher..These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis. ..
- O Neill L. A Metabolic Roadblock in Inflammatory Macrophages. Cell Rep. 2016;17:625-626 pubmed publisher..2016) reveal that, once the M1 macrophage forms, the accompanying metabolic alterations in the mitochondria are irreversible, preventing differentiation into the more homeostatic M2 macrophage. ..
- O Neill L. Toll-like receptor signal transduction and the tailoring of innate immunity: a role for Mal?. Trends Immunol. 2002;23:296-300 pubmed..These findings may ultimately explain how dendritic cells control specific T-cell responses. ..
- Domingo Fernández R, Coll R, Kearney J, Breit S, O Neill L. The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1? transcription and activate the NLRP3 inflammasome. J Biol Chem. 2017;292:12077-12087 pubmed publisher..Collectively, our results demonstrate that CLIC1 and CLIC4 participate both in the priming signal for IL-1? and in NLRP3 activation. ..
- Palsson McDermott E, Curtis A, Goel G, Lauterbach M, Sheedy F, Gleeson L, et al. Pyruvate kinase M2 regulates Hif-1? activity and IL-1? induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015;21:65-80 pubmed publisher..PKM2 is therefore a critical determinant of macrophage activation by LPS, promoting the inflammatory response. ..
- Wochal P, Rathinam V, Dunne A, Carlson T, Kuang W, Seidl K, et al. TRIL is involved in cytokine production in the brain following Escherichia coli infection. J Immunol. 2014;193:1911-9 pubmed publisher..coli and LPS challenge. Collectively, these data uncover TRIL as a mediator of innate immune responses within the brain, where it enhances neuronal cytokine responses to infection. ..
- O Neill L. Innate immunity: squelching anti-viral signalling with NLRX1. Curr Biol. 2008;18:R302-4 pubmed publisher..Recent work has identified that NLRX1, a member of another class of innate immune receptors, sequesters MAVS away from RIG-I and thereby prevents mitochondrial anti-viral immunity. ..
- O Neill L, Bowie A. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7:353-64 pubmed..These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling. ..