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FAT NKT SIGNED

Targeting iNKT cell and adipocyte crosstalk for control of metabolism and body weight

Total Cost €

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EC-Contrib. €

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Partnership

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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
address: College Green
city: DUBLIN
postcode: 2
website: www.tcd.ie

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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 Clancy‐Thompson, Gui Zhen Chen, Nelson M LaMarche, Lestat R Ali, Hee‐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 B‐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, Róisín 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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