a mathematical model for the reciprocal differentiation of t helper 17 cells and induced regulatory t cells一个数学模型相互17辅助t细胞的分化和诱导调节性t细胞.pdfVIP

A Mathematical Model for the Reciprocal Differentiation of T Helper 17 Cells and Induced Regulatory T Cells 1 2 2 2 Tian Hong , Jianhua Xing , Liwu Li , John J. Tyson * 1 Genetics, Bioinformatics, and Computational Biology Program, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 2 Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America Abstract The reciprocal differentiation of T helper 17 (TH17) cells and induced regulatory T (iTreg) cells plays a critical role in both the pathogenesis and resolution of diverse human inflammatory diseases. Although initial studies suggested a stable commitment to either the TH17 or the iTreg lineage, recent results reveal remarkable plasticity and heterogeneity, reflected in the capacity of differentiated effectors cells to be reprogrammed among TH17 and iTreg lineages and the intriguing ¨ + phenomenon that a group of naıve precursor CD4 T cells can be programmed into phenotypically diverse populations by the same differentiation signal, transforming growth factor beta. To reconcile these observations, we have built a mathematical model of TH17/iTreg differentiation that exhibits four different stable steady states, governed by pitchfork bifurcations with certain degrees of broken symmetry. According to the model, a group of precursor cells with some small cell-to-cell variability can differentiate into phenotypically distinct subsets of cells, which exhibit distinct levels of the master transcription-factor regu