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• W2040636315 endingPage "49" @default.
• W2040636315 startingPage "41" @default.
• W2040636315 abstract "The maintenance of self-tolerance is an integral part of the immune surveillance process, in which cytokines act as master regulators of a complex network involving multiple cell types. On such cytokines, transforming growth factor-β (TGF-β) exerts a suppressive control over immune reactivity, which so far appears to be mostly confined to the T-cell compartment. Recently, dendritic cells (DCs) have been found to be both an early source and a target of TGF-β actions. In these cells, autocrine, paracrine and T-cell-derived TGF-β activates the tolerogenic pathway of tryptophan catabolism – mediated by indoleamine 2,3-dioxygenase (IDO) – resulting in a burst of regulatory kynurenines that contribute to establishing a state of ‘infectious tolerance’. Current molecular insights suggest a synergistic potential for TGF-β and IDO in physiologically or therapeutically opposing human pathologies sustained by over-reacting immune responses. The maintenance of self-tolerance is an integral part of the immune surveillance process, in which cytokines act as master regulators of a complex network involving multiple cell types. On such cytokines, transforming growth factor-β (TGF-β) exerts a suppressive control over immune reactivity, which so far appears to be mostly confined to the T-cell compartment. Recently, dendritic cells (DCs) have been found to be both an early source and a target of TGF-β actions. In these cells, autocrine, paracrine and T-cell-derived TGF-β activates the tolerogenic pathway of tryptophan catabolism – mediated by indoleamine 2,3-dioxygenase (IDO) – resulting in a burst of regulatory kynurenines that contribute to establishing a state of ‘infectious tolerance’. Current molecular insights suggest a synergistic potential for TGF-β and IDO in physiologically or therapeutically opposing human pathologies sustained by over-reacting immune responses. the terms ‘counter-receptor’ and ‘coreceptor’ have distinct conventional meanings in different contexts. Counter-receptor often indicates the complementary molecule that binds to an adhesion molecule in a structurally specific manner. A coreceptor might instead be a second cell-surface receptor required for the entry of a pathogen into a host cell or initiation of a biological process (as in the case of HIV). It is also a protein that increases the sensitivity of an antigen receptor or neurotransmitter receptor to its ligand by binding to regulatory molecules (as for the glycine receptor, which modulates the N-methyl-D-aspartate [NMDA] glutamatergic receptor). In lymphocyte activation, a coreceptor is defined as a signaling receptor that directly associates with the very same antigen that is seen by the antigen receptor (CD3ζ and T-cell receptor). In reverse signaling, and as used in this context, a pair of coreceptors is represented by molecules on adjacent cells that reciprocally act as ligands and receptors. these are dendritic cells in which indoleamine 2,3-dioxygenase (IDO) is not transcriptionally expressed or, more often, the enzyme is not catalytically active due to post-translational changes, absence of necessary ‘cofactors’ or presence of inhibitors. The term is often used to indicate cells in which the first and limiting (IDO-mediated) step of tryptophan catabolism is inhibited, yet the downstream enzymes are functional and active if supplied with their own kynurenine substrate. these are dendritic cells in which IDO is expressed and functionally active (IDO-competent DCs). In these cells, via a mechanism driven by reverse signaling, tryptophan can be transformed into metabolites termed ‘kynurenines’. these are regulatory T cells whose differentiation is driven by TGF-β from naïve T cells in peripheral tissues. iTreg cells are characterized by suppressive activity typically associated with Foxp3 expression. this term is used to generically refer to all intermediate and final products of tryptophan catabolism, named after l-kynurenine, the initial amino acid metabolite produced by IDO action on tryptophan. these are regulatory T cells that differentiate early in the thymus in a TGF-β-dependent fashion. due to primary ligands having evolved into ancillary receptors, a mechanism of intercellular communication has emerged during evolution (‘reverse signaling’) that enables a ligand-bearing cell to receive an immediate feedback upon activation of the cognate receptor on an adjacent cell. The term reverse signaling was introduced into immunology to indicate a two-way communication between cells or cell types via a single pair of transducing molecules – acting reciprocally as ligands and receptors (‘coreceptors’) – whereby information actually flows in both directions, but one direction (‘forward’) has been of greater or longer-standing importance. More recently, reverse and noncanonical signaling has been used to indicate regulatory T-cell conditioning of dendritic cells (DCs) via costimulatory ligands that, expressed by DCs, transduce intracellular signals back into the DCs, where they activate noncanonical nuclear factor-κB." @default.
• W2040636315 created "2016-06-24" @default.
• W2040636315 creator A5011703773 @default.
• W2040636315 creator A5021481850 @default.
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• W2040636315 date "2009-02-01" @default.
• W2040636315 modified "2023-10-05" @default.
• W2040636315 title "TGF-β and kynurenines as the key to infectious tolerance" @default.
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