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      B Vitamins and Their Role in Immune Regulation and Cancer

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          Abstract

          B group vitamins represent essential micronutrients for myriad metabolic and regulatory processes required for human health, serving as cofactors used by hundreds of enzymes that carry out essential functions such as energy metabolism, DNA and protein synthesis and other critical functions. B vitamins and their corresponding vitamers are universally essential for all cellular life forms, from bacteria to humans. Humans are unable to synthesize most B vitamins and are therefore dependent on their diet for these essential micronutrients. More recently, another source of B vitamins has been identified which is derived from portions of the 10 13 bacterial cells inhabiting the gastrointestinal tract. Here we review the expanding literature examining the relationship between B vitamins and the immune system and diverse cancers. Evidence of B vitamin’s role in immune cell regulation has accumulated in recent years and may help to clarify the disparate findings of numerous studies attempting to link B vitamins to cancer development. Much work remains to be carried out to fully clarify these relationships as the complexity of B vitamins’ essential functions complicates an unequivocal assessment of their beneficial or detrimental effects in inflammation and cancers.

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          Most cited references145

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          Metabolic Instruction of Immunity.

          Choices have consequences. Immune cells survey and migrate throughout the body and sometimes take residence in niche environments with distinct communities of cells, extracellular matrix, and nutrients that may differ from those in which they matured. Imbedded in immune cell physiology are metabolic pathways and metabolites that not only provide energy and substrates for growth and survival, but also instruct effector functions, differentiation, and gene expression. This review of immunometabolism will reference the most recent literature to cover the choices that environments impose on the metabolism and function of immune cells and highlight their consequences during homeostasis and disease.
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            T-cell activation by transitory neo-antigens derived from distinct microbial pathways.

            T cells discriminate between foreign and host molecules by recognizing distinct microbial molecules, predominantly peptides and lipids. Riboflavin precursors found in many bacteria and yeast also selectively activate mucosal-associated invariant T (MAIT) cells, an abundant population of innate-like T cells in humans. However, the genesis of these small organic molecules and their mode of presentation to MAIT cells by the major histocompatibility complex (MHC)-related protein MR1 (ref. 8) are not well understood. Here we show that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-d-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis. Although 5-A-RU does not bind MR1 or activate MAIT cells directly, it does form potent MAIT-activating antigens via non-enzymatic reactions with small molecules, such as glyoxal and methylglyoxal, which are derived from other metabolic pathways. The MAIT antigens formed by the reactions between 5-A-RU and glyoxal/methylglyoxal were simple adducts, 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), respectively, which bound to MR1 as shown by crystal structures of MAIT TCR ternary complexes. Although 5-OP-RU and 5-OE-RU are unstable intermediates, they became trapped by MR1 as reversible covalent Schiff base complexes. Mass spectra supported the capture by MR1 of 5-OP-RU and 5-OE-RU from bacterial cultures that activate MAIT cells, but not from non-activating bacteria, indicating that these MAIT antigens are present in a range of microbes. Thus, MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells. These pyrimidine adducts are microbial signatures for MAIT-cell immunosurveillance.
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              Immunometabolism: an emerging frontier.

              Immunometabolism is an emerging field of investigation at the interface between the historically distinct disciplines of immunology and metabolism. Accelerating interest in this area is being fuelled by the obesity epidemic and the relatively recent realization that obesity affects the immune system and promotes inflammation, and that obesity-induced inflammation potentially promotes a variety of chronic conditions and diseases. The multilevel interactions between the metabolic and immune systems suggest pathogenic mechanisms that may underlie many of the downstream complications of obesity and offer substantial therapeutic promise.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                04 November 2020
                November 2020
                : 12
                : 11
                : 3380
                Affiliations
                [1 ]Center of Excellence for Research and Training in Integrative Health, Department of Family Medicine and Public Health, UC San Diego, School of Medicine, La Jolla, CA 92093, USA; chpeterson@ 123456ucsd.edu
                [2 ]Bioinformatics and Structural Biology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; rodionov@ 123456SBPdiscovery.org
                [3 ]A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, 119991 Moscow, Russia
                [4 ]Immunity and Pathogenesis Program, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; osterman@ 123456SBPdiscovery.org
                [5 ]Tumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
                Author notes
                Author information
                https://orcid.org/0000-0002-0939-390X
                Article
                nutrients-12-03380
                10.3390/nu12113380
                7693142
                33158037
                e32dceba-ec7b-4281-bdfb-2832ef269aef
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 October 2020
                : 02 November 2020
                Categories
                Review

                Nutrition & Dietetics
                thiamine,riboflavin,niacin,pantothenic acid,pyridoxine,biotin,folate,cobalamin,gut microbiota,inflammation,oxidative stress,cancer

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