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Role of glucose and serine metabolism in regulating the CD8+ T cell memory response

English title Role of glucose and serine metabolism in regulating the CD8+ T cell memory response
Applicant Hess Christoph
Number 172848
Funding scheme Project funding (Div. I-III)
Research institution Departement Biomedizin Universität Basel
Institution of higher education University of Basel - BS
Main discipline Immunology, Immunopathology
Start/End 01.04.2017 - 31.03.2021
Approved amount 850'000.00
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Keywords (5)

immunometabolism; immunology; transcriptional regulation; glucose and serine metabolism; memory CD8+ T cells

Lay Summary (German)

Lead
Die Rolle des Zucker- und Aminosäuren-Stoffwechsels in der ImmunantwortChristoph Hess
Lay summary

Gedächtniszellen schützen uns vor wiederkehrenden Infektionen. Der Zellstoffwechsel unserer Gedächtniszellen spielt eine zentrale Rolle nicht nur in der Bereitstellung von Energie sondern auch als Regulator zellulärer Funktionen. Aufbauend auf unseren Arbeiten zum Zellstoffwechsel der Gedächtniszellen möchten wir in diesem Projekt definieren wie sich der Stoffwechsel des Gesamtorganismus im Rahmen von Infektionen verändert und wie diese Veränderungen sich auf zellulärer Ebene auswirken. Basierend auf Daten aus Vorversuchen wird unser Fokus auf dem Zucker- und Aminosäuren (insbes. Serin)-Stoffwechsel sein. Von einem präzisen Verständnis wie der Stoffwechsel des Gesamtorganismus den Zellstoffwechsel der Gedächtniszellen beeinflusst –und dadurch zelluläre Funktionen verändert– erwarten wir Hinweise für gezielte metabolische Interventionen.

Direct link to Lay Summary Last update: 10.11.2017

Responsible applicant and co-applicants

Project partner

Publications

Publication
Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages
Dowling Jennifer K., Afzal Remsha, Gearing Linden J., Cervantes-Silva Mariana P., Annett Stephanie, Davis Gavin M., De Santi Chiara, Assmann Nadine, Dettmer Katja, Gough Daniel J., Bantug Glenn R., Hamid Fidinny I., Nally Frances K., Duffy Conor P., Gorman Aoife L., Liddicoat Alex M., Lavelle Ed C., Hess Christoph, Oefner Peter J., Finlay David K., Davey Gavin P., Robson Tracy, Curtis Annie M., Hertzog Paul J., et al. (2021), Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages, in Nature Communications, 12(1), 1460-1460.
Reference Genes for Expression Studies in Human CD8+ Naïve and Effector Memory T Cells under Resting and Activating Conditions
Geigges Marco, Gubser Patrick M., Unterstab Gunhild, Lecoultre Yannic, Paro Renato, Hess Christoph (2020), Reference Genes for Expression Studies in Human CD8+ Naïve and Effector Memory T Cells under Resting and Activating Conditions, in Scientific Reports, 10(1), 9411-9411.
Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells
Rivers Elizabeth, Rai Rajeev, Lötscher Jonas, Hollinshead Michael, Markelj Gasper, Thaventhiran James, Worth Austen, Cavazza Alessia, Hess Christoph, Bajaj-Elliott Mona, Thrasher Adrian J (2020), Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells, in eLife, 9, e55547-e55547.
Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection
Balmer Maria L., Ma Eric H., Thompson Andrew J., Epple Raja, Unterstab Gunhild, Lötscher Jonas, Dehio Philippe, Schürch Christian M., Warncke Jan D., Perrin Gaëlle, Woischnig Anne-Kathrin, Grählert Jasmin, Löliger Jordan, Assmann Nadine, Bantug Glenn R., Schären Olivier P., Khanna Nina, Egli Adrian, Bubendorf Lukas, Rentsch Katharina, Hapfelmeier Siegfried, Jones Russell G., Hess Christoph (2020), Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection, in Cell Metabolism, 32(3), 457-467.e5.
Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity
Künzli Marco, Schreiner David, Pereboom Tamara C., Swarnalekha Nivedya, Litzler Ludivine C., Lötscher Jonas, Ertuna Yusuf I., Roux Julien, Geier Florian, Jakob Roman P., Maier Timm, Hess Christoph, Taylor Justin J., King Carolyn G. (2020), Long-lived T follicular helper cells retain plasticity and help sustain humoral immunity, in Science Immunology, 5(45), eaay5552-eaay5552.
Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells
Kolev Martin, West Erin E., Kunz Natalia, Chauss Daniel, Moseman E. Ashley, Rahman Jubayer, Freiwald Tilo, Balmer Maria L., Lötscher Jonas, Dimeloe Sarah, Rosser Elizabeth C., Wedderburn Lucy R., Mayer-Barber Katrin D., Bohrer Andrea, Lavender Paul, Cope Andrew, Wang Luopin, Kaplan Mariana J., Moutsopoulos Niki M., McGavern Dorian, Holland Steven M., Hess Christoph, Kazemian Majid, Afzali Behdad, et al. (2020), Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells, in Immunity, 52(3), 513-527.e8.
Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge
Brykczynska Urszula, Geigges Marco, Wiedemann Sophia J., Dror Erez, Böni-Schnetzler Marianne, Hess Christoph, Donath Marc Y., Paro Renato (2020), Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge, in Cell Reports, 30(5), 1627-1643.e7.
JAK2-mutant hematopoietic cells display metabolic alterations that can be targeted to treat myeloproliferative neoplasms
Rao Tata Nageswara, Hansen Nils, Hilfiker Julian, Rai Shivam, Majewska Julia-Magdalena, Leković Danijela, Gezer Deniz, Andina Nicola, Galli Serena, Cassel Teresa, Geier Florian, Delezie Julien, Nienhold Ronny, Hao-Shen Hui, Beisel Christian, Di Palma Serena, Dimeloe Sarah, Trebicka Jonel, Wolf Dominik, Gassmann Max, Fan Teresa W.-M., Lane Andrew N., Handschin Christoph, Dirnhofer Stefan, et al. (2019), JAK2-mutant hematopoietic cells display metabolic alterations that can be targeted to treat myeloproliferative neoplasms, in Blood, 134(21), 1832-1846.
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza Andrea, Chang Hyun‐Dong, Radbruch Andreas, Acs Andreas, Adam Dieter, Adam‐Klages Sabine, Agace William W., Aghaeepour Nima, Akdis Mübeccel, Allez Matthieu, Almeida Larissa Nogueira, Alvisi Giorgia, Anderson Graham, Andrä Immanuel, Annunziato Francesco, Anselmo Achille, Bacher Petra, Baldari Cosima T., Bari Sudipto, Barnaba Vincenzo, Barros‐Martins Joana, Battistini Luca, Bauer Wolfgang, Baumgart Sabine, et al. (2019), Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition), in European Journal of Immunology, 49(10), 1457-1973.
SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2
Burgener Anne-Valérie, Bantug Glenn R., Meyer Benedikt J., Higgins Rebecca, Ghosh Adhideb, Bignucolo Olivier, Ma Eric H., Loeliger Jordan, Unterstab Gunhild, Geigges Marco, Steiner Rebekah, Enamorado Michel, Ivanek Robert, Hunziker Danielle, Schmidt Alexander, Müller-Durovic Bojana, Grählert Jasmin, Epple Raja, Dimeloe Sarah, Lötscher Jonas, Sauder Ursula, Ebnöther Monika, Burger Bettina, Heijnen Ingmar, et al. (2019), SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2, in Nature Immunology, 20(10), 1311-1321.
Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4 + T cells
Dimeloe Sarah, Gubser Patrick, Loeliger Jordan, Frick Corina, Develioglu Leyla, Fischer Marco, Marquardsen Florian, Bantug Glenn R., Thommen Daniela, Lecoultre Yannic, Zippelius Alfred, Langenkamp Anja, Hess Christoph (2019), Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4 + T cells, in Science Signaling, 12(599), eaav3334-eaav3334.
The power of description
Hess Christoph (2019), The power of description, in Nature Reviews Immunology, 19(8), 475-475.
CD56-negative NK cells with impaired effector function expand in CMV and EBV co-infected healthy donors with age
Müller-Durovic Bojana, Grählert Jasmin, Devine Oliver P., Akbar Arne N., Hess Christoph (2019), CD56-negative NK cells with impaired effector function expand in CMV and EBV co-infected healthy donors with age, in Aging, 11(2), 724-740.
Gain Fat—Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis
Ishay-Ronen Dana, Diepenbruck Maren, Kalathur Ravi Kiran Reddy, Sugiyama Nami, Tiede Stefanie, Ivanek Robert, Bantug Glenn, Morini Marco Francesco, Wang Junrong, Hess Christoph, Christofori Gerhard (2019), Gain Fat—Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis, in Cancer Cell, 35(1), 17-32.e6.
Early effector maturation of naïve human CD8 + T cells requires mitochondrial biogenesis
Fischer Marco, Bantug Glenn R., Dimeloe Sarah, Gubser Patrick M., Burgener Anne-Valérie, Grählert Jasmin, Balmer Maria L., Develioglu Leyla, Steiner Rebekah, Unterstab Gunhild, Sauder Ursula, Hoenger Gideon, Hess Christoph (2018), Early effector maturation of naïve human CD8 + T cells requires mitochondrial biogenesis, in European Journal of Immunology, 48(10), 1632-1643.
The heart in systemic lupus erythematosus – A comprehensive approach by cardiovascular magnetic resonance tomography
Burkard Thilo, Trendelenburg Marten, Daikeler Thomas, Hess Christoph, Bremerich Jens, Haaf Philip, Buser Peter, Zellweger Michael J. (2018), The heart in systemic lupus erythematosus – A comprehensive approach by cardiovascular magnetic resonance tomography, in PLOS ONE, 13(10), e0202105-e0202105.
A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade
Thommen Daniela S., Koelzer Viktor H., Herzig Petra, Roller Andreas, Trefny Marcel, Dimeloe Sarah, Kiialainen Anna, Hanhart Jonathan, Schill Catherine, Hess Christoph, Savic Prince Spasenija, Wiese Mark, Lardinois Didier, Ho Ping-Chih, Klein Christian, Karanikas Vaios, Mertz Kirsten D., Schumacher Ton N., Zippelius Alfred (2018), A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade, in Nature Medicine, 24(7), 994-1004.
Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients
Quteineh Lina, Wójtowicz Agnieszka, Bochud Pierre‐Yves, Crettol Severine, Vandenberghe Frederik, Venetz Jean‐Pierre, Manuel Oriol, Golshayan Dela, Lehmann Roger, Mueller Nicolas J., Binet Isabelle, Delden Christian, Steiger Jürg, Mohacsi Paul, Dufour Jean‐Francois, Soccal Paola M., Kutalik Zoltan, Marques‐Vidal Pedro, Vollenweider Peter, Recher Mike, Hess Christoph, Pascual Manuel, Eap Chin B. (2018), Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients, in American Journal of Transplantation, 19(1), 238-246.
Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8+ T Cells
Bantug Glenn R., Fischer Marco, Grählert Jasmin, Balmer Maria L., Unterstab Gunhild, Develioglu Leyla, Steiner Rebekah, Zhang Lianjun, Costa Ana S.H., Gubser Patrick M., Burgener Anne-Valérie, Sauder Ursula, Löliger Jordan, Belle Réka, Dimeloe Sarah, Lötscher Jonas, Jauch Annaïse, Recher Mike, Hönger Gideon, Hall Michael N., Romero Pedro, Frezza Christian, Hess Christoph (2018), Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8+ T Cells, in Immunity, 48(3), 542-555.e6.
The spectrum of T cell metabolism in health and disease
Bantug Glenn R., Galluzzi Lorenzo, Kroemer Guido, Hess Christoph (2018), The spectrum of T cell metabolism in health and disease, in Nature Reviews Immunology, 18(1), 19-34.
Detection of Sp110 by Flow Cytometry and Application to Screening Patients for Veno-occlusive Disease with Immunodeficiency
Marquardsen Florian A., Baldin Fabian, Wunderer Florian, Al-Herz Waleed, Mikhael Raymond, Lefranc Gérard, Baz Zeina, Rezaee Fariba, Hanna Rabi, Kfir-Erenfeld Shlomit, Stepensky Polina, Meyer Benedikt, Jauch Annaise, Bigler Marc B., Burgener Anne-Valérie, Higgins Rebecca, Navarini Alexander A., Church Joeseph A., Chou Janet, Geha Raif, Notarangelo Luigi D., Hess Christoph, Berger Christoph T., Bloch Donald B., et al. (2017), Detection of Sp110 by Flow Cytometry and Application to Screening Patients for Veno-occlusive Disease with Immunodeficiency, in Journal of Clinical Immunology, 37(7), 707-714.
The Burgeoning World of Immunometabolites: Th17 Cells Take Center Stage
Bantug Glenn R., Hess Christoph (2017), The Burgeoning World of Immunometabolites: Th17 Cells Take Center Stage, in Cell Metabolism, 26(4), 588-590.
Starving for survival—how catabolic metabolism fuels immune function
Balmer Maria L, Hess Christoph (2017), Starving for survival—how catabolic metabolism fuels immune function, in Current Opinion in Immunology, 46, 8-13.
Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage
Schürmann Nura, Forrer Pascal, Casse Olivier, Li Jiagui, Felmy Boas, Burgener Anne-Valérie, Ehrenfeuchter Nikolaus, Hardt Wolf-Dietrich, Recher Mike, Hess Christoph, Tschan-Plessl Astrid, Khanna Nina, Bumann Dirk (2017), Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage, in Nature Microbiology, 2(4), 16268-16268.
Vedolizumab as a successful treatment of CTLA-4–associated autoimmune enterocolitis
Navarini Alexander A., Hruz Petr, Berger Christoph T., Hou Tie Zheng, Schwab Charlotte, Gabrysch Annemarie, Higgins Rebecca, Frede Natalie, Padberg Sgier Barbara-Christina, Kämpe Olle, Burgener Anne-Valérie, Marquardsen Florian, Baldin Fabian, Bigler Marc, Kistner Anne, Jauch Annaise, Bignucolo Olivier, Meyer Benedikt, Meienberg Fabian, Mehling Matthias, Jeker Lukas T., Heijnen Ingmar, Daikeler Thomas D., Gebbers Jan-Olaf, et al. (2017), Vedolizumab as a successful treatment of CTLA-4–associated autoimmune enterocolitis, in Journal of Allergy and Clinical Immunology, 139(3), 1043-1046.e5.
HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells
Li Qingxue, Bu Wei, Gabriel Erin, Aguilar Fiona, Hoshino Yo, Miyadera Hiroko, Hess Christoph, Hornung Ronald L., Roy Amitava, Cohen Jeffrey I. (2017), HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells, in JCI Insight, 2(4), n/a-n/a.
Serine Is an Essential Metabolite for Effector T Cell Expansion
Ma Eric H., Bantug Glenn, Griss Takla, Condotta Stephanie, Johnson Radia M., Samborska Bozena, Mainolfi Nello, Suri Vipin, Guak Hannah, Balmer Maria L., Verway Mark J., Raissi Thomas C., Tsui Harmony, Boukhaled Giselle, Henriques da Costa Sofia, Frezza Christian, Krawczyk Connie M., Friedman Adam, Manfredi Mark, Richer Martin J., Hess Christoph, Jones Russell G. (2017), Serine Is an Essential Metabolite for Effector T Cell Expansion, in Cell Metabolism, 25(2), 345-357.
T-cell metabolism governing activation, proliferation and differentiation; a modular view
Dimeloe Sarah, Burgener Anne-Valérie, Grählert Jasmin, Hess Christoph (2017), T-cell metabolism governing activation, proliferation and differentiation; a modular view, in Immunology, 150(1), 35-44.

Scientific events



Self-organised

Title Date Place
Translational Immunometabolism 24.06.2019 Basel, Switzerland

Associated projects

Number Title Start Funding scheme
189780 Multidimensional immune profiling of single cells using mass cytometry 01.01.2020 R'EQUIP
153059 Metabolic regulation of the memory CD8+ T cell response 01.04.2014 Project funding (Div. I-III)
160766 Immunologic consequences of time-graded exposure to an 'obesity-diabetes milieu' 01.08.2015 Sinergia

Abstract

Memory CD8 T cells form the cellular basis for accelerated protection upon re-exposure to the same pathogen, which is a hallmark of adaptive immunity. Reprogramming of metabolic pathways in activated memory T cells is intricately linked to their function. The metabolic basis enabling augmented immune function of memory CD8 T cells during re-infection remains ill explored. Nutrient abundance in the extracellular milieu is altered during infection. How metabolite alterations in the microenvironment influence memory CD8 T cell responses has not been sufficiently investigated.We recently identified both serine and glucose as critical determinants of the CD8 T cell memory response, in vitro and in vivo. We now wish to define how serine and glucose metabolism impacts the CD8 T cell memory response at the organismal, cellular, biochemical, subcellular, and transcriptional level.
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