A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity
Fig 3
CD4+ T cell transcriptional-signaling regulatory network (TSRN).
We constructed a regulatory network using available experimental data. The network includes transcription factors, signaling pathways, and intrinsic and extrinsic cytokines. (A) Graph of the TSRN. The nodes include transcription factors (rectangles), intrinsic cytokines and their signaling pathways (ellipses) and extrinsic cytokines (ellipses). Node colors correspond to cell type: Th1 (yellow), Th2 (green), Th17 (red), iTreg (blue), Tfh (purple), and Th9 (brown). Activations between elements are represented with black arrows, and inhibitions with red dotted arrows. The dotted lines represent inhibition mediated by SOCS proteins. (B) Attractors of the TSRN. Each column corresponds to an attractor. Each node can be active (green) or inactive (red), extrinsic cytokines may be active or inactive (yellow). The following attractors were found in the network: Th0, Th1, Th2, Th17, iTreg, Tfh, Th9 producing T cells, Foxp3-independent T regulatory cells (TrFoxp3-), T-bet+ T regulatory cells (Th1R), GATA3+ T regulatory cells (Th2R) and GATA3+IL-4- cells. Attractors where labeled according to the active transcription factors and intrinsic cytokines.