mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity

Author:

Cheng Shih-Chin1,Quintin Jessica1,Cramer Robert A.2,Shepardson Kelly M.2,Saeed Sadia3,Kumar Vinod4,Giamarellos-Bourboulis Evangelos J.5,Martens Joost H. A.3,Rao Nagesha Appukudige3,Aghajanirefah Ali3,Manjeri Ganesh R.6,Li Yang4,Ifrim Daniela C.1,Arts Rob J. W.1,van der Veer Brian M. J. W.4,Deen Peter M. T.7,Logie Colin3,O’Neill Luke A.8,Willems Peter6,van de Veerdonk Frank L.1,van der Meer Jos W. M.1,Ng Aylwin910,Joosten Leo A. B.1,Wijmenga Cisca4,Stunnenberg Hendrik G.4,Xavier Ramnik J.910,Netea Mihai G.1

Affiliation:

1. Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.

2. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

3. Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.

4. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

5. 4th Department of Internal Medicine, University of Athens Medical School, 12462 Athens, Greece.

6. Department of Biochemistry, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.

7. Department of Physiology, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.

8. School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.

9. Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA.

10. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Abstract

A BLUEPRINT of immune cell development To determine the epigenetic mechanisms that direct blood cells to develop into the many components of our immune system, the BLUEPRINT consortium examined the regulation of DNA and RNA transcription to dissect the molecular traits that govern blood cell differentiation. By inducing immune responses, Saeed et al. document the epigenetic changes in the genome that underlie immune cell differentiation. Cheng et al. demonstrate that trained monocytes are highly dependent on the breakdown of sugars in the presence of oxygen, which allows cells to produce the energy needed to mount an immune response. Chen et al. examine RNA transcripts and find that specific cell lineages use RNA transcripts of different length and composition (isoforms) to form proteins. Together, the studies reveal how epigenetic effects can drive the development of blood cells involved in the immune system. Science , this issue 10.1126/science.1251086 , 10.1126/science.1250684 , 10.1126/science.1251033

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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