Robustness trade‐offs and host–microbial symbiosis in the immune system

Kitano, Hiroaki; Oda, Kanae

doi:10.1038/msb4100039

Cited by 117 publications

(104 citation statements)

References 88 publications

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“…The maintenance of homeostatic stability, while concurrently monitoring environmental perturbations, is an essential property of the immune system-one that is believed to derive from modularity of components and incorporation of control via feedback (32,33). The capability of T cells to access multiple programs for cytokine release allows diverse and dynamically evolvable contributions to the sustained accumulation of cytokines in the global milieu, and such behavior represents an intriguing manifestation of modularity, cell-to-cell communication, and feedback.…”

Section: Discussionmentioning

confidence: 99%

Polyfunctional responses by human T cells result from sequential release of cytokines

Han¹,

Bagheri

Bradshaw

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

289

298

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The release of cytokines by T cells defines a significant part of their functional activity in vivo, and their ability to produce multiple cytokines has been associated with beneficial immune responses. To date, time-integrated end-point measurements have obscured whether these polyfunctional states arise from the simultaneous or successive release of cytokines. Here, we used serial, timedependent, single-cell analysis of primary human T cells to resolve the temporal dynamics of cytokine secretion from individual cells after activation ex vivo. We show that multifunctional, Th1-skewed cytokine responses (IFN-γ, IL-2, TNFα) are initiated asynchronously, but the ensuing dynamic trajectories of these responses evolve programmatically in a sequential manner. That is, cells predominantly release one of these cytokines at a time rather than maintain active secretion of multiple cytokines simultaneously. Furthermore, these dynamic trajectories are strongly associated with the various states of cell differentiation suggesting that transient programmatic activities of many individual T cells contribute to sustained, population-level responses. The trajectories of responses by single cells may also provide unique, time-dependent signatures for immune monitoring that are less compromised by the timing and duration of integrated measures.microengraving | multifunctionality | dynamical systems | computational biology

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Section: Discussionmentioning

confidence: 99%

Polyfunctional responses by human T cells result from sequential release of cytokines

Han¹,

Bagheri

Bradshaw

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

289

298

View full text Add to dashboard Cite

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“…The nodes in the fan-in wing are sources of flow into the core, whereas the nodes in the fan-out wing, also called sinks, receive flow from the core. Bowtie topologies have been observed to occur both in man-made networks such as the (Broder et al 2000;Kleinberg and Lawrence 2001), the Internet (Tauro et al 2001;Siganos et al 2006), manufacturing processes (Csete and Doyle 2004) and biological systems (Csete and Doyle 2004;Kitano 2004), including metabolism (Ma and Zeng 2003;Ma et al 2007), the immune system (Kitano and Oda 2006) and cell signaling (Natarajan et al 2006;Supper et al 2009). The reason for the widespread occurrence of this type of structural organization is possibly due to the fact that highly functional systems are also non-equilibrium systems (in a thermodynamic sense) and, as such, they have to maintain energy and matter flow through the system to optimize their functionality.…”

Section: The Cortical Core-periphery Structurementioning

confidence: 99%

The Brain in Space

Knoblauch

Ercsey-Ravasz

Kennedy

et al. 2016

Micro-, Meso- And Macro-Connectomics of the Brain

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Recent connectomic tract tracing reveals that, contrary to what was previously thought, the cortical inter-areal network has high density. This finding leads to a necessary revision of the relevance of some of the graph theoretical notions, such as the small-world property, hubs and rich-clubs that have been claimed to characterize the inter-areal cortical network. Weight and projection distance relationships of inter-areal connections inferred from consistent tract tracing data have recently led to the definition of a novel network model, the exponential distance rule (EDR) model, that predicts many observed local and global features of the cortex. The EDR model is a spatially embedded network whose properties are determined by the physical constraints on wiring and geometry, in sharp contrast with the purely topological graph models used heretofore in the description of the cortex. We speculate that, when diving down to finer levels of the embedded cortical network, similar, physically constrained descriptions of connectivity may prove to be equally important for understanding cortical function.

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“…From the standard biochemical point of view, the metabolic system is organized as a bow-tie whose knot is made up of a small handful of activated carriers and 12 precursors, with a large "fan-in" of nutrients, and a large "fan-out" of products in biosynthetic pathways [20,23] . Such organization pattern has been reported to be present in various biological systems, such as in signal transduction systems, transcription and translation processes, and immune systems [20,23,26,[39][40][41] . The bow-tie model here could give alternative view of the biological metabolite flow from the topological aspects, where the knot is much thicker than that of above.…”

Section: Significance Of Bow-tie Topology To Metabolismmentioning

confidence: 99%

Bow-tie topological features of metabolic networks and the functional significance

Zhao

Lin

et al. 2007

Chin. Sci. Bull.

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Exploring the structural topology of genome-based large-scale metabolic network is essential for investigating possible relations between structure and functionality. Visualization would be helpful for obtaining immediate information about structural organization. In this work, metabolic networks of 75 organisms were investigated from a topological point of view. A spread bow-tie model was proposed to give a clear visualization of the bow-tie structure for metabolic networks. The revealed topological pattern helps to design more efficient algorithm specifically for metabolic networks. This coarse-grained graph also visualizes the vulnerable connections in the network, and thus could have important implication for disease studies and drug target identifications. In addition, analysis on the reciprocal links and main cores in the GSC part of bow-tie also reveals that the bow-tie structure of metabolic networks has its own intrinsic and significant features which are significantly different from those of random networks.Keywords: bioinformatics; metabolic network; bow-tie; random network.As the results of various genome projects, the genome sequences of many organisms are available and the organism specific metabolic networks can be faithfully reconstructed from genome information [1][2][3][4][5][6] . Thus the prediction of function from the metabolic networks has become an essential step in the post-genomic era [4,[7][8][9][10][11] . However, before it is possible to investigate the potential relationship between structure and functionality of a metabolic network, it is necessary to study how the metabolic networks are actually constructed.In recent years there has been a strongly increasing passion in investigating the intricate structures of link topologies in metabolic networks [12][13][14][15][16][17][18][19][20][21] . Many researchers have applied methods from graph theory to treat the metabolic networks as a directed graph consisting of nodes denoting metabolites connected by directed arcs representing reactions. An important finding is that metabolic networks, as well as other real-world complex networks, have topologies that differ markedly from those found in simple randomly connected networks [22] , which suggests that their non-random structures could imply significant organizing principles of metabolic networks.From the computational analysis of genome-based metabolic networks of 65 organisms, Ma and Zeng discovered that the global metabolic network is organized in the form of a bow-tie [15] . On the other hand, from the view of material flows and information flows in the metabolic system, Csete and Doyle described metabolism as several nested bow-ties [23] . It was pointed out that bow-tie architectures facilitate robust biologic function, and based on their design, also have

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Robustness trade‐offs and host–microbial symbiosis in the immune system

Cited by 117 publications

References 88 publications

Polyfunctional responses by human T cells result from sequential release of cytokines

Polyfunctional responses by human T cells result from sequential release of cytokines

The Brain in Space

Bow-tie topological features of metabolic networks and the functional significance

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