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Archive

Publications

Some of the latest publications from our group are linked below.

Immunometabolic adaptation in monocytes underpins functional changes during pregnancy

April Rees, Benjamin J. Jenkins, Roberto Angelini, Luke C. Davies, James G. Cronin, Nicholas Jones, Catherine A. Thornton

Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met, might also underpin changes in immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Using peripheral blood from pregnant women at term, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration, and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism, then show in pregnancy reduced cytokine production in response to MDP but not LPS. Overall, mitochondrially centered metabolic capabilities of late gestation monocytes are down-regulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield alternative therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.

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The dynamic inflammatory profile of pregnancy can be monitored using a novel lipid-based mass spectrometry technique

The lipid environment changes throughout pregnancy both physiologically with emergent insulin resistance and pathologically e.g., gestational diabetes mellitus (GDM). Novel mass spectrometry (MS) techniques applied to minimally processed blood might lend themselves to monitoring changing lipid profiles to inform care decisions across pregnancy. In this study we use an intact-sandwich, MALDI-ToF MS method to identify phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) species and calculate their ratio as an indicator of inflammation. Plasma and sera were prepared from venous blood of non-pregnant women (aged 18-40) and pregnant women at 16 weeks, 28 weeks (including GDM-positive women), and 37+ weeks (term) of gestation alongside umbilical cord blood (UCB). Women with a normal menstrual cycle and age-matched men provided finger-prick derived capillary sera at 6 time-points over a month. Serum rather than plasma was preferable for PC/LPC measurement. As pregnancy progresses, an anti-inflammatory phenotype dominates the maternal circulation, evidenced by increasing PC/LPC ratio. In contrast, the PC/LPC ratio of UCB was aligned to that of non-pregnant donors. BMI had no significant effect on the PC/LPC ratio, but GDM-complicated pregnancies had significantly lower PC/LPC at 16 weeks of gestation. To further translate the use of the PC/LPC ratio clinically, the utility of finger-prick blood was evaluated; no significant difference between capillary versus venous serum was found and we revealed the PC/LPC ratio oscillates with the menstrual cycle. Overall, we show that the PC/LPC ratio can be measured simply in human serum and has the potential to be used as a time-efficient and less invasive biomarker of (mal)adaptative inflammation.

Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation

Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.

List of publications with current lab members as authors.

Listed back to 2020 - for more publications please see authors' orcids.

2024.

Rees A, Jenkins BJ, Angelini R, Davies LC, Cronin JG, Jones N, Thornton CA.

Farook MR, Croxford Z, Morgan S, Horlock AD, Holt AK, Rees A, Jenkins BJ, Tse C, Stanton E, Davies DM, Thornton CA, Jones N, Sheldon IM, Vincent EE, Cronin JG.​

​Ravelojaona M, Girouard J, Kana Tsapi ES, Chambers M, Vaillancourt C, Van Themsche C, Thornton CA, Reyes-Moreno C.

2023.

Jenkins BJ, Blagih J, Ponce-Garcia FM, Canavan M, Gudgeon N, Eastham S, Hill D, Hanlon MM, Ma EH, Bishop EL, Rees A, Cronin JG, Jury EC, Dimeloe SK, Veale DJ, Thornton CA, Vousden KH, Finlay DK, Fearon U, Jones GW, Sinclair LV, Vincent EE, Jones N.

​Dickson A, Yutuc E, Thornton CA, Dunford JE, Oppermann U, Wang Y, Griffiths WJ.

​Rees A, Edwards-I-Coll Z, Richards O, Raikes ME, Angelini R, Thornton CA.

2022.

Evans BA, Akbari A, Bailey R, Bethell L, Bufton S, Carson-Stevens A, Dixon L, Edwards A, John A, Jolles S, Kingston MR, Lyons J, Lyons R, Porter A, Sewell B, Thornton CA, Watkins A, Whiffen T, Snooks H.

Dickson AL, Yutuc E, Thornton CA, Wang Y, Griffiths WJ.

Rees A, Richards O, Chambers M, Jenkins BJ, Cronin JG, Thornton CA.

Rees A, Richards O, Allen-Kormylo A, Jones N, Thornton CA.

2021.

Richards O, Jenkins C, Griffiths H, Paczkowska E, Dunstan PR, Jones S, Morgan M, Thomas T, Bowden J, Nakimuli A, Nair M, Thornton CA.

​Jenkins BJ, Rees A, Jones N, Thornton CA.

Rees A, Turner S, Thornton CA.

​Ahmed Z, Powell LC, Matin N, Mearns-Spragg A, Thornton CA, Khan IM, Francis LW.

​Wills JW, Verma JR, Rees BJ, Harte DSG, Haxhiraj Q, Barnes CM, Barnes R, Rodrigues MA, Doan M, Filby A, Hewitt RE, Thornton CA, Cronin JG, Kenny JD, Buckley R, Lynch AM, Carpenter AE, Summers HD, Johnson GE, Rees P.

Holm SR, Jenkins BJ, Cronin JG, Jones NThornton CA.​

​Jones N, Blagih J, Zani F, Rees A, Hill DG, Jenkins BJ, Bull CJ, Moreira D, Bantan AIM, Cronin JG, Avancini D, Jones GW, Finlay DK, Vousden KH, Vincent EE, Thornton CA.

​Chambers M, Rees A, Cronin JG, Nair M, Jones N, Thornton CA.

2020.

Skevaki C, Thornton CA.

Jovic TH, Ali SR, Ibrahim N, Jessop ZM, Tarassoli SP, Dobbs TD, Holford P, Thornton CA, Whitaker IS.

Sala A, Spalding KE, Ashton KM, Board R, Butler HJ, Dawson TP, Harris DA, Hughes CS, Jenkins CA, Jenkinson MD, Palmer DS, Smith BR, Thornton CA, Baker MJ.

Thomas BR, Hambly RJ, Weisel JW, Rauova L, Badiei N, Brown MR, Thornton CA, Williams PR, Hawkins K.

Jessop ZM, Al-Sabah A, Simoes IN, Burnell SEA, Pieper IL, Thornton CA, Whitaker IS.

Cronin JG, Jones N, Thornton CA, Jenkins GJS, Doak SH, Clift MJD.

Jones N, Vincent EE, Felix LC, Cronin JG, Scott LM, Hole PS, Lacy P, Thornton CA.

Radley G, Pieper IL, Robinson CR, Ali S, Beshr M, Bodger O, Thornton CA.

Piasecka J, Thornton CA, Rees P, Summers HD.

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