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      Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing

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          Abstract

          Metabolism is dynamically regulated to accompany immune cell function, and altered immunometabolism can result in impaired immune responses. Concomitantly, the pharmacological manipulation of metabolic processes offers an opportunity for therapeutic intervention in inflammatory disorders. The nicotinamide adenine dinucleotide (NAD +) is a critical metabolic intermediate that serves as enzyme cofactor in redox reactions, and is also used as a co‐substrate by many enzymes such as sirtuins, adenosine diphosphate ribose transferases and synthases. Through these activities, NAD + metabolism regulates a broad spectrum of cellular functions such as energy metabolism, DNA repair, regulation of the epigenetic landscape and inflammation. Thus, the manipulation of NAD + availability using pharmacological compounds such as NAD + precursors can have immune‐modulatory properties in inflammation. Here, we discuss how the NAD + metabolism contributes to the immune response and inflammatory conditions, with a special focus on multiple sclerosis, inflammatory bowel diseases and inflammageing.

          LINKED ARTICLES

          This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc

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          Most cited references153

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          Multiple sclerosis

          The Lancet, 372(9648), 1502-1517
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            Immunopathology of multiple sclerosis.

            Two decades of clinical experience with immunomodulatory treatments for multiple sclerosis point to distinct immunological pathways that drive disease relapses and progression. In light of this, we discuss our current understanding of multiple sclerosis immunopathology, evaluate long-standing hypotheses regarding the role of the immune system in the disease and delineate key questions that are still unanswered. Recent and anticipated advances in the field of immunology, and the increasing recognition of inflammation as an important component of neurodegeneration, are shaping our conceptualization of disease pathophysiology, and we explore the potential implications for improved healthcare provision to patients in the future.
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              Gut microbiota and IBD: causation or correlation?

              A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host–microbial relationships relevant to human disease and amenable to therapeutic interventions.
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                Author and article information

                Contributors
                marian.navarro@cbm.csic.es
                mmittelbrunn@cbm.csic.es
                Journal
                Br J Pharmacol
                Br J Pharmacol
                10.1111/(ISSN)1476-5381
                BPH
                British Journal of Pharmacology
                John Wiley and Sons Inc. (Hoboken )
                0007-1188
                1476-5381
                12 May 2021
                May 2022
                12 May 2021
                : 179
                : 9 , Themed Issue: Inflammation, Repair and Ageing ( doiID: 10.1111/bph.v179.9 )
                : 1839-1856
                Affiliations
                [ 1 ] Interactions With The Environment Program, Immune System Development and Function Unit, Centro de Biología Molecular “Severo Ochoa” (CBMSO) Consejo Superior de Investigaciones Científicas (CSIC)‐Universidad Autónoma de Madrid (UAM) Madrid Spain
                [ 2 ] Departamento de Biología Molecular, Centro de Biología Molecular “Severo Ochoa” (CBMSO) Consejo Superior de Investigaciones Científicas (CSIC)‐Universidad Autónoma de Madrid (UAM) Madrid Spain
                [ 3 ] Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12) Madrid Spain
                Author notes
                [*] [* ] Correspondence

                Maria N. Navarro, Interactions With The Environment Program, Immune System Development and Function Unit, Centro de Biología Molecular “Severo Ochoa” (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC)‐Universidad Autónoma de Madrid (UAM), Madrid, Spain.

                Email: marian.navarro@ 123456cbm.csic.es

                Maria Mittelbrunn, Departamento de Biología Molecular, Centro de Biología Molecular “Severo Ochoa” (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC)‐Universidad Autónoma de Madrid (UAM), Madrid, Spain.

                Email: mmittelbrunn@ 123456cbm.csic.es

                Author information
                https://orcid.org/0000-0003-3977-812X
                https://orcid.org/0000-0001-7447-694X
                https://orcid.org/0000-0003-3487-8762
                Article
                BPH15477
                10.1111/bph.15477
                9292562
                33817782
                c2bd0702-633b-412c-ad9c-03252084d957
                © 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 24 March 2021
                : 11 January 2021
                : 26 March 2021
                Page count
                Figures: 5, Tables: 0, Pages: 18, Words: 19630
                Funding
                Funded by: Spanish Ministry of Science and Innovation , doi 10.13039/501100004837;
                Award ID: PID2019‐110511RB‐I00 to M.N.N
                Funded by: Spanish Ministry of Science, Innovation and Universities
                Award ID: FPU19/02576 to M.M.GH
                Funded by: H2020 European Research Council , doi 10.13039/100010663;
                Award ID: ERC‐2016‐StG 715322‐EndoMitTalk to M.M
                Funded by: Fondo de Investigación Sanitaria del Instituto de Salud Carlos III
                Award ID: PI19/855 to M.M
                Funded by: Miguel Servet program
                Award ID: CPII19/00014 to M.M
                Funded by: Fondo Europeo de Desarrollo Regional (FEDER) to M.M and M.N.N , doi 10.13039/501100008530;
                Funded by: Banco de Santander
                Funded by: Fundación Ramón Areces , doi 10.13039/100008054;
                Categories
                Commissioned Review Article ‐ Themed Issue
                Inflammation, Repair and Ageing ‐ Review Article
                Custom metadata
                2.0
                May 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:18.07.2022

                Pharmacology & Pharmaceutical medicine
                ageing,cd38,experimental autoimmune encephalomyelitis,inflammation,lymphocytes,nad+ ,t cells

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