Dietary tryptophan deficiency promotes gut RORγt+ Treg cells at the expense of Gata3+ Treg cells and alters commensal microbiota metabolism. 2023

Lucille C Rankin, and Katherine A Kaiser, and Kenia de Los Santos-Alexis, and Heekuk Park, and Anne-Catrin Uhlemann, and Daniel H D Gray, and Nicholas Arpaia
Department of Microbiology & Immunology, Columbia University Irving Medical Center, 701 West 168th Street, HHSC 910C, New York, NY, USA; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.

Micronutrient deficiency is a major cause of disease throughout the world. Yet, how perturbations influence the immune-microbiome interface remains poorly understood. Here, we report that loss of dietary tryptophan (Trp) reshapes intestinal microbial communities, including the depletion of probiotic L. reuteri, drives transcriptional changes to immune response genes in the intestinal ileum, and reshapes the regulatory T cell (Treg) compartment. Dietary Trp deficiency promotes expansion of RORγt+ Treg cells and the loss of Gata3+ Tregs in a microbiota-dependent manner. In the absence of dietary Trp, provision of the AhR ligand indole-3-carbinol is sufficient to restore the Treg compartment. Together, these data show that dietary Trp deficiency perturbs the interaction between the host and its bacterial symbionts to regulate Treg homeostasis via the deprivation of bacterially derived Trp metabolites. Our findings highlight an essential role for immune-microbiome crosstalk as a key homeostatic regulator during nutrient deficiency.

UI MeSH Term Description Entries
D006706 Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Autoregulation
D014364 Tryptophan An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. Ardeydorm,Ardeytropin,L-Tryptophan,L-Tryptophan-ratiopharm,Levotryptophan,Lyphan,Naturruhe,Optimax,PMS-Tryptophan,Trofan,Tryptacin,Tryptan,Tryptophan Metabolism Alterations,ratio-Tryptophan,L Tryptophan,L Tryptophan ratiopharm,PMS Tryptophan,ratio Tryptophan
D050378 T-Lymphocytes, Regulatory CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells. Regulatory T Cell,Regulatory T-Cell,Regulatory T-Lymphocyte,Regulatory T-Lymphocytes,Suppressor T-Lymphocytes, Naturally-Occurring,T-Cells, Regulatory,Th3 Cells,Tr1 Cell,Treg Cell,Regulatory T-Cells,Suppressor T-Cells, Naturally-Occurring,Tr1 Cells,Treg Cells,Cell, Regulatory T,Cell, Th3,Cell, Tr1,Cell, Treg,Cells, Regulatory T,Cells, Th3,Cells, Tr1,Cells, Treg,Naturally-Occurring Suppressor T-Cell,Naturally-Occurring Suppressor T-Cells,Naturally-Occurring Suppressor T-Lymphocyte,Naturally-Occurring Suppressor T-Lymphocytes,Regulatory T Cells,Regulatory T Lymphocyte,Regulatory T Lymphocytes,Suppressor T Cells, Naturally Occurring,Suppressor T Lymphocytes, Naturally Occurring,Suppressor T-Cell, Naturally-Occurring,Suppressor T-Lymphocyte, Naturally-Occurring,T Cell, Regulatory,T Cells, Regulatory,T Lymphocytes, Regulatory,T-Cell, Naturally-Occurring Suppressor,T-Cells, Naturally-Occurring Suppressor,T-Lymphocyte, Regulatory,Th3 Cell
D057132 Nuclear Receptor Subfamily 1, Group F, Member 3 An orphan nuclear receptor found in the THYMUS where it plays a role in regulating the development and maturation of thymocytes. An isoform of this protein, referred to as RORgammaT, is produced by an alternatively transcribed mRNA. Nuclear Receptor NR1F3,Nuclear Receptor RZR-gamma,Orphan Nuclear Receptor NR1F3,Orphan Nuclear Receptor ROR-gamma,Orphan Nuclear Receptor ROR-gammaT,RAR-related Orphan Receptor C,ROR-C Receptors,ROR-gamma,ROR-gammat,RORgammaT,Nuclear Receptor RZR gamma,Orphan Nuclear Receptor ROR gamma,Orphan Nuclear Receptor ROR gammaT,RAR related Orphan Receptor C,ROR C Receptors,Receptor NR1F3, Nuclear,Receptor RZR-gamma, Nuclear
D018336 Receptors, Aryl Hydrocarbon Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected. AH Receptors,Aryl Hydrocarbon Receptors,Dioxin Receptors,Receptors, AH,Receptors, Dioxin,TCDD Receptors,AH Receptor,Aryl Hydrocarbon Receptor,Dioxin Receptor,Polyaromatic Hydrocarbon Receptor,Polyaromatic Hydrocarbon Receptors,Receptors, 2,3,7,8-Tetrachlorodibenzo-p-dioxin,Receptors, Polyaromatic Hydrocarbon,Receptors, TCDD,TCDD Receptor,Receptor, AH,Receptor, Aryl Hydrocarbon,Receptor, Dioxin,Receptor, Polyaromatic Hydrocarbon,Receptor, TCDD
D064307 Microbiota The full collection of microbes (bacteria, fungi, virus, etc.) that naturally exist within a particular biological niche such as an organism, soil, a body of water, etc. Human Microbiome,Microbiome,Microbiome, Human,Microbial Community,Microbial Community Composition,Microbial Community Structure,Community Composition, Microbial,Community Structure, Microbial,Community, Microbial,Composition, Microbial Community,Human Microbiomes,Microbial Communities,Microbial Community Compositions,Microbial Community Structures,Microbiomes,Microbiotas

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