FAT NKT SIGNED
Targeting iNKT cell and adipocyte crosstalk for control of metabolism and body weight
Total Cost €
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Project "FAT NKT" data sheet
The following table provides information about the project.
| Coordinator |
THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Organization address contact info |
| Coordinator Country | Ireland [IE] |
| Total cost | 1˙804˙052 € |
| EC max contribution | 1˙804˙052 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-09-01 to 2021-08-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN | IE (DUBLIN) | coordinator | 1˙804˙052.00 |
Map
Project objective
Obesity has reached epidemic proportions globally. At least 2.8 million people die each year as a result of being overweight or obese, the biggest burden being obesity-related diseases. It is now clear that inflammation is an underlying cause or contributor to many of these diseases, including type 2 diabetes, atherosclerosis, and cancer. Recognition that the immune system can regulate metabolic pathways has prompted a new way of thinking about diabetes and weight management. Despite much recent progress, most immunometabolic pathways, and how to target them, are currently unknown. One such pathway is the cross-talk between invariant natural killer (iNKT) cells and neighboring adipocytes. iNKT cells are the innate lipid-sensing arm of the immune system. Since our discovery that mammalian adipose tissue is enriched for iNKT cells, we have identified a critical role for iNKT cells in regulating adipose inflammation and body weight. The goal of this project is to use a multi-disciplinary approach to identify key signals and molecules used by iNKT cells to induce metabolic control and weight loss in obesity. Using immunological assays and multi-photon intravital microscopy, cells and pathways that control the unique regulatory functions of adipose iNKT cells will be identified and characterised. Novel lipid antigens in adipose tissue will be identified using a biochemical approach, perhaps explaining iNKT cell conservation in adipose depots, and providing safe tools for iNKT cell manipulation in vivo. Finally, using proteomics and whole body metabolic analysis in vivo, novel ‘weight-loss inducing’ factors produced by adipose iNKT cells will be identified. This ambitious and high impact project has the potential to yield major insights into immunometabolic interactions at steady state and in obesity. The ability to activate or induce adipose iNKT cells holds remarkable potential as an entirely new therapeutic direction for treating obesity and type 2 diabetes.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2018 |
Lydia Dyck, Lydia Lynch Cancer, obesity and immunometabolism – Connecting the dots published pages: 11-20, ISSN: 0304-3835, DOI: 10.1016/j.canlet.2017.12.019 |
Cancer Letters 417 | 2019-10-08 |
| 2018 |
Xavier Michelet, Lydia Dyck, Andrew Hogan, Roisin M. Loftus, Danielle Duquette, Kevin Wei, Semir Beyaz, Ali Tavakkoli, Cathriona Foley, Raymond Donnelly, Cliona O’Farrelly, Mathilde Raverdeau, Ashley Vernon, William Pettee, Donal O’Shea, Barbara S. Nikolajczyk, Kingston H. G. Mills, Michael B. Brenner, David Finlay, Lydia Lynch Metabolic reprogramming of natural killer cells in obesity limits antitumor responses published pages: 1330-1340, ISSN: 1529-2908, DOI: 10.1038/s41590-018-0251-7 |
Nature Immunology 19/12 | 2019-10-08 |
| 2016 |
Ayano C. Kohlgruber, Nelson M. LaMarche, Lydia Lynch Adipose tissue at the nexus of systemic and cellular immunometabolism published pages: 431-440, ISSN: 1044-5323, DOI: 10.1016/j.smim.2016.09.005 |
Seminars in Immunology 28/5 | 2019-10-08 |
| 2018 |
Shangyu Hong, Wei Song, Peter-James H. Zushin, Bingyang Liu, Mark P. Jedrychowski, Amir I. Mina, Zhaoming Deng, Dimitrije Cabarkapa, Jessica A. Hall, Colin J. Palmer, Hassan Aliakbarian, John Szpyt, Steven P. Gygi, Ali Tavakkoli, Lydia Lynch, Norbert Perrimon, Alexander S. Banks Phosphorylation of Beta-3 adrenergic receptor at serine 247 by ERK MAP kinase drives lipolysis in obese adipocytes published pages: 25-38, ISSN: 2212-8778, DOI: 10.1016/j.molmet.2018.03.012 |
Molecular Metabolism 12 | 2019-10-08 |
| 2019 |
Aisling O’Brien, Roisin M. Loftus, Marta M. Pisarska, Laura M. Tobin, Ronan Bergin, Nicole A. W. Wood, Cathriona Foley, Arimin Mat, Frances C. Tinley, Ciaran Bannan, Gary Sommerville, Natacha Veerapen, Gurdyal S. Besra, Linda V. Sinclair, Paul N. Moynagh, Lydia Lynch, David K. Finlay, Donal O’Shea, Andrew E. Hogan Obesity Reduces mTORC1 Activity in Mucosal-Associated Invariant T Cells, Driving Defective Metabolic and Functional Responses published pages: 3404-3411, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1801600 |
The Journal of Immunology 202/12 | 2019-10-08 |
| 2018 |
Di Wu, Di Hu, Hao Chen, Guoming Shi, Irfete S. Fetahu, Feizhen Wu, Kimberlie Rabidou, Rui Fang, Li Tan, Shuyun Xu, Hang Liu, Christian Argueta, Lei Zhang, Fei Mao, Guoquan Yan, Jiajia Chen, Zhaoru Dong, Ruitu Lv, Yufei Xu, Mei Wang, Yong Ye, Shike Zhang, Danielle Duquette, Songmei Geng, Clark Yin, Christine Guo Lian, George F. Murphy, Gail K. Adler, Rajesh Garg, Lydia Lynch, Pengyuan Yang, Yiming Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer published pages: 637-641, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0350-5 |
Nature 559/7715 | 2019-10-08 |
| 2018 |
Nelson M. LaMarche, Lydia Lynch Adipose Dendritic Cells Come Out of Hiding published pages: 485-486, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.02.014 |
Cell Metabolism 27/3 | 2019-10-08 |
| 2018 |
Lydia Dyck, Lydia Lynch New Job for NK Cells: Architects of the Tumor Microenvironment published pages: 9-11, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2018.01.001 |
Immunity 48/1 | 2019-10-08 |
| 2019 |
Harry Kane, Lydia Lynch Innate Immune Control of Adipose Tissue Homeostasis published pages: 857-872, ISSN: 1471-4906, DOI: 10.1016/j.it.2019.07.006 |
Trends in Immunology 40/9 | 2019-10-08 |
| 2019 |
Eleanor Clancyâ€Thompson, Gui Zhen Chen, Nelson M LaMarche, Lestat R Ali, Heeâ€Jin Jeong, Stephanie J Crowley, Kelly Boelaars, Michael B Brenner, Lydia Lynch, Stephanie K Dougan Transnuclear mice reveal Peyer\'s patch iNKT cells that regulate Bâ€cell class switching to IgG1 published pages: , ISSN: 0261-4189, DOI: 10.15252/embj.2018101260 |
The EMBO Journal 38/14 | 2019-10-08 |
| 2018 |
Ayano C. Kohlgruber, Shani T. Gal-Oz, Nelson M. LaMarche, Moto Shimazaki, Danielle Duquette, Hung N. Nguyen, Amir I. Mina, Tyler Paras, Ali Tavakkoli, Ulrich von Andrian, Alexander S. Banks, Tal Shay, Michael B. Brenner, Lydia Lynch γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis published pages: 464-474, ISSN: 1529-2908, DOI: 10.1038/s41590-018-0094-2 |
Nature Immunology 19/5 | 2019-06-19 |
| 2017 |
Selma Boulenouar, Xavier Michelet, Danielle Duquette, David Alvarez, Andrew E. Hogan, Christina Dold, Donal O’Connor, Suzanne Stutte, Ali Tavakkoli, Desmond Winters, Mark A. Exley, Donal O’Shea, Michael B. Brenner, Ulrich von Andrian, Lydia Lynch Adipose Type One Innate Lymphoid Cells Regulate Macrophage Homeostasis through Targeted Cytotoxicity published pages: 273-286, ISSN: 1074-7613, DOI: 10.1016/j.immuni.2017.01.008 |
Immunity 46/2 | 2019-06-19 |
| 2016 |
Lydia Lynch, Andrew E. Hogan, Danielle Duquette, Chantel Lester, Alexander Banks, Katherine LeClair, David E. Cohen, Abhisek Ghosh, Bing Lu, Michelle Corrigan, Darko Stevanovic, Eleftheria Maratos-Flier, Daniel J. Drucker, Donal O’Shea, Michael Brenner iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy published pages: 510-519, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2016.08.003 |
Cell Metabolism 24/3 | 2019-06-19 |
| 2017 |
Sook Kyung Chang, Ayano C. Kohlgruber, Fumitaka Mizoguchi, Xavier Michelet, Benjamin J. Wolf, Kevin Wei, Pui Y. Lee, Lydia Lynch, Danielle Duquette, Victòria Ceperuelo-Mallafré, Alexander S. Banks, Michael B. Brenner Stromal cell cadherin-11 regulates adipose tissue inflammation and diabetes published pages: 3300-3312, ISSN: 0021-9738, DOI: 10.1172/JCI86881 |
Journal of Clinical Investigation 127/9 | 2019-06-19 |
| 2017 |
Nadine Assmann, Katie L O\'Brien, Raymond P Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, RóisÃn M Loftus, Paul Heinrich, Peter J Oefner, Lydia Lynch, Clair M Gardiner, Katja Dettmer, David K Finlay Srebp-controlled glucose metabolism is essential for NK cell functional responses published pages: 1197-1206, ISSN: 1529-2908, DOI: 10.1038/ni.3838 |
Nature Immunology 18/11 | 2019-06-19 |
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