Figure 9.

Summary of the interrelationships between the major biological themes defining the alterations in the extracellular milieu during the emergence of Sjögren’s syndrome. Time points are aligned in correspondence with the chronology of the development of major features of Sjögren’s syndrome in C57BL/6.NOD-Aec1Aec2 mice [8]. Plotted on the y-axis is the cumulative number of leading edge (LE) genes (solid lines) associated with enrichment and depletion of the respective summarized biological theme over time. The right y-axis represents the same parameter, but for the LE genes specifically located in the disease-causing congenic loci Aec1 and Aec2 (dashed lines). The summarized biological theme Immunity comprises the themes Innate immunity (Figure 3) and Adaptive immunity (Figure 6). The summarized biological theme Focal adhesion and motility, cell–cell junctions and cytoskeleton organization comprises the themes Focal adhesion and motility (Figure 3), Gap junctions (Figure 5) and Focal adhesion and cell-cell junctions (Figure 7). The summarized biological theme Insr/Igfr1 signaling comprises the theme Insr/Igfr1 signaling (Figure 3). The summarized biological theme ECM turnover comprises the themes ECM turnover (Figure 5) and Collagen I and III (Additional file 1: Figure S2). The summarized biological theme Neurotransmission comprises the themes Neurotransmission in Figures 5 and 6. ECM, extracellular matrix.