Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring DOI Creative Commons
Valentina Pucino, Michelangelo Certo, Vinay Bulusu

et al.

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(6), P. 1055 - 1074.e8

Published: Nov. 7, 2019

Accumulation of lactate in the tissue microenvironment is a feature both inflammatory disease and cancer. Here, we assess response immune cells to context chronic inflammation. We report that accumulation inflamed contributes upregulation transporter SLC5A12 by human CD4+ T cells. SLC5A12-mediated uptake into induces reshaping their effector phenotype, resulting increased IL17 production via nuclear PKM2/STAT3 enhanced fatty acid synthesis. It also leads cell retention as consequence reduced glycolysis Furthermore, antibody-mediated blockade ameliorates severity murine model arthritis. Finally, propose lactate/SLC5A12-induced metabolic reprogramming distinctive lymphoid synovitis rheumatoid arthritis patients potential therapeutic target disorders.

Language: Английский

Mitochondrial TCA cycle metabolites control physiology and disease DOI Creative Commons
Inmaculada Martínez‐Reyes, Navdeep S. Chandel

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 3, 2020

Abstract Mitochondria are signaling organelles that regulate a wide variety of cellular functions and can dictate cell fate. Multiple mechanisms contribute to communicate mitochondrial fitness the rest cell. Recent evidence confers new role for TCA cycle intermediates, generally thought be important biosynthetic purposes, as molecules with controlling chromatin modifications, DNA methylation, hypoxic response, immunity. This review summarizes by which abundance different metabolites controls function fate in contexts. We will focus on how these mediated affect physiology disease.

Language: Английский

Citations

1890

Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? DOI Creative Commons
Tamàs Fülöp, Anis Larbi, Gilles Dupuis

et al.

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 8

Published: Jan. 9, 2018

The immune system is the most important protective physiological of organism. It has many connections with other systems and is, in fact, often considered as part larger neuro-endocrine-immune axis. Most experimental data on changes aging show a decline parameters when compared to young healthy subjects. bulk these termed immunosenescence. Immunosenescence been for some time detrimental because it leads subclinical accumulation proinflammatory factors inflamm-aging. Together, immunosenescence inflamm-aging are suggested stand at origin diseases elderly, such infections, cancer, autoimmune disorders, chronic inflammatory diseases. However, an increasing number immune-gerontologists have challenged this negative interpretation respect its significance aging-related alterations system. If one considers from evolutionary perspective, they can be viewed preferably adaptive or remodeling rather than solely detrimental. Whereas conceivable that global may lead various diseases, also obvious needed extended survival/longevity. Recent cumulative suggest that, without existence immunosenescence/inflamm-aging duo (representing two sides same phenomenon), human longevity would greatly shortened. This review summarizes recent dynamic reassessment aging. Accordingly, attempts intervene by targeting rejuvenation, more suitable aim maintain general homeostasis function appropriately improving immune-inflammatory-functions.

Language: Английский

Citations

1096

Metabolic Instruction of Immunity DOI Creative Commons
Michael D. Buck, Ryan Sowell,

Susan M. Kaech

et al.

Cell, Journal Year: 2017, Volume and Issue: 169(4), P. 570 - 586

Published: May 1, 2017

Language: Английский

Citations

993

Mitochondria are the powerhouses of immunity DOI
Evanna L. Mills, Beth Kelly, Luke O'neill

et al.

Nature Immunology, Journal Year: 2017, Volume and Issue: 18(5), P. 488 - 498

Published: April 18, 2017

Language: Английский

Citations

869

Chromatin states define tumour-specific T cell dysfunction and reprogramming DOI
Mary Philip, Lauren Fairchild, Liping Sun

et al.

Nature, Journal Year: 2017, Volume and Issue: 545(7655), P. 452 - 456

Published: May 1, 2017

Language: Английский

Citations

794

Lactate metabolism in human health and disease DOI Creative Commons
Xiaolu Li, Yanyan Yang, Bei Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 1, 2022

Abstract The current understanding of lactate extends from its origins as a byproduct glycolysis to role in tumor metabolism, identified by studies on the Warburg effect. shuttle hypothesis suggests that plays an important bridging signaling molecule coordinates among different cells, organs and tissues. Lactylation is posttranslational modification initially reported Professor Yingming Zhao’s research group 2019. Subsequent confirmed lactylation vital component function involved proliferation, neural excitation, inflammation other biological processes. An indispensable substance for various physiological cellular functions, regulatory aspects energy metabolism signal transduction. Therefore, comprehensive review summary presented clarify disease provide reference direction future research. This offers systematic overview homeostasis roles pathological processes, well effects diseases, particularly cancer.

Language: Английский

Citations

670

Unraveling the Complex Interplay Between T Cell Metabolism and Function DOI Open Access
Ramon I. Klein Geltink, Ryan Kyle, Erika L. Pearce

et al.

Annual Review of Immunology, Journal Year: 2018, Volume and Issue: 36(1), P. 461 - 488

Published: April 20, 2018

Metabolism drives function, on both an organismal and a cellular level. In T cell biology, metabolic remodeling is intrinsically linked to development, activation, differentiation, survival. After naive cells are activated, increased demands for currency in the form of ATP, as well biomass growth, proliferation, production effector molecules, met by rewiring metabolism. Consequently, pharmacological strategies being developed perturb or enhance selective processes that skewed immune-related pathologies. Here we review most recent advances describing changes occur during lifecycle. We discuss how metabolism can have profound effects health disease where it might be promising target treat variety

Language: Английский

Citations

666

Lactate modulation of immune responses in inflammatory versus tumour microenvironments DOI
Michelangelo Certo, Chin‐Hsien Tsai, Valentina Pucino

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 21(3), P. 151 - 161

Published: Aug. 24, 2020

Language: Английский

Citations

568

Distinct Regulation of Th17 and Th1 Cell Differentiation by Glutaminase-Dependent Metabolism DOI Creative Commons

Marc O. Johnson,

Melissa M. Wolf, Matthew Z. Madden

et al.

Cell, Journal Year: 2018, Volume and Issue: 175(7), P. 1780 - 1795.e19

Published: Nov. 1, 2018

Language: Английский

Citations

560

Metabolic coordination of T cell quiescence and activation DOI
Nicole M. Chapman, Mark Boothby, Hongbo Chi

et al.

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(1), P. 55 - 70

Published: Aug. 12, 2019

Language: Английский

Citations

558