title: Continuous time Bayesian networks identify Prdm1 as a negative regulator of TH17 cell differentiation in humans.
abstract: T helper 17 (TH17) cells represent a pivotal adaptive cell subset involved in multiple immune disorders in mammalian species. Deciphering the molecular interactions regulating TH17 cell differentiation is particularly critical for novel drug target discovery designed to control maladaptive inflammatory conditions. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling TH17 differentiation. From the network, we identified the Prdm1 gene encoding the B lymphocyte-induced maturation protein 1 as a crucial negative regulator of human TH17 cell differentiation. The results have been validated by perturbing Prdm1 expression on freshly isolated CD4(+) naïve T cells: reduction of Prdm1 expression leads to augmentation of IL-17 release. These data unravel a possible novel target to control TH17 polarization in inflammatory disorders. Furthermore, this study represents the first in vitro validation of continuous time Bayesian networks as gene network reconstruction method and as hypothesis generation tool for wet-lab biological experiments.
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (Nanyang Technological University), Singapore 637551.|Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos #04-06, Singapore 138648.
authors.forename: Enzo
authors.initials: E
authors.lastname: Acerbi
authors.affiliation: Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos #04-06, Singapore 138648.
authors.forename: Elena
authors.initials: E
authors.lastname: Viganò
authors.affiliation: Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos #04-06, Singapore 138648.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos #04-06, Singapore 138648.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
authors.affiliation: Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.|Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos #04-06, Singapore 138648.
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.affiliation: Department of Informatics, Systems and Communication, University of Milano-Bicocca, Viale Sarca 336, Building U14, 20126 Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Stella
mesh_terms: D001499:Bayes Theorem; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1