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Bioinformatics Advance Access published online on December 21, 2004
Bioinformatics, doi:10.1093/bioinformatics/bti239
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Bioinformatics © Oxford University Press 2004; all rights reserved.
Received September 20, 2004
Revised December 10, 2004
Accepted December 16, 2004

Article

Quantifying the relevance of different mediators in the human immune cell network

P. Tieri 1, S. Valensin 2, V. Latora 3, G. C. Castellani 2, M. Marchiori 4, D. Remondini 2, and C. Franceschi 5*

1 Dipartimento di Patologia Sperimentale, Università di Bologna, Via San Giacomo 12, 40126 Bologna, Italy
2 C.I.G. - Centro Interdipartimentale "L. Galvani" per Studi Integrati di Bioinformatica, Biofisica e Biocomplessità, Università di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Italy
3 Dipartimento di Fisica ed Astronomia and INFN - Istituto Nazionale Fisica Nucleare, Università di Catania, Via S. Sofia 64, 95123 Catania, Italy
4 W3C MIT Lab for Computer Science, 545 Technology Square, Cambridge, MA 02139, USA; Dipartimento di Informatica, Università di Venezia, Via Torino 155, 30172 Mestre, Italy
5 Dipartimento di Patologia Sperimentale, Università di Bologna, Via San Giacomo 12, 40126 Bologna, Italy; C.I.G. - Centro Interdipartimentale "L. Galvani" per Studi Integrati di Bioinformatica, Biofisica e Biocomplessità, Università di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia, Italy; INRCA - Istituto Nazionale di Ricovero e Cura Anziani, Dipartimento Ricerche, Via Birarelli 8, 60100 Ancona, Italy

* To whom correspondence should be addressed.
C. Franceschi, E-mail: claudio.franceschi{at}unibo.it


  Abstract

Motivation: Immune cells coordinate their efforts for the correct and efficient functioning of the immune system (IS). Each cell type plays a distinct role and communicates with other cell types through mediators such as cytokines, chemokines and hormones, among others, that are crucial for the functioning of the IS and its fine tuning. Nevertheless, a quantitative analysis of the topological properties of an immunological network involving this complex interchange of mediators among immune cells is still lacking.

Results: Here we present a method for quantifying the relevance of different mediators in the immune network, which exploits a definition of centrality based on the concept of efficient communication. The analysis, applied to the human immune system, indicates that its mediators significantly differ in their network relevance. We found that cytokines involved in innate immunity and inflammation and some hormones rank highest in the network, revealing that the most prominent mediators of the IS are molecules involved in these ancestral types of defence mechanisms highly integrated with the adaptive immune response, and at the interplay among the nervous, the endocrine and the immune systems.


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