Reconstruction of Intercellular Signaling Network by Cytokine-Receptor Interactions

BACKGROUND: The immune system function depends on the coordination activity of the components of system and communications between them which leads to the formation of a complex communication network between immune cells. In this network, cytokines have an important role in the communication between immune cells through the interaction to their specific receptors. These molecules cause to cellular communications and normal function of a tissue. Reconstruction of such a complex network can be a way to provide a better understanding of cytokines’ function. OBJECTIVE: Our main goal from reconstructing such a network was investigation of expressed cytokines and cytokines receptors in various lineage and tissues of immune cells and identifying the lineage and tissue with the highest expression of cytokines and their receptors. MATERIALS AND METHODS: In this study, gene expression data related to part of the Immunological Genome Project (ImmGen) and receptor-ligand interactions dataset were used to reconstruct the immune network in mouse. In next step, the topological properties of reconstructed network, expression specificity of cytokines and their receptors and interactions specificity were analyzed. RESULTS: The results of the network analysis were indicated that non- hematopoietic stromal cells have the highest expression of cytokines and cytokine receptors and interactions specificity is very high. Our results show that chemokine receptor of Ccr1 receives the largest number of signals between receptors and only expressed in three hematopoietic lineages. CONCLUSIONS: The most of the network communications belonged to non-hematopoietic stromal and macrophage cells. The relationships between stromal cells and macrophages are necessary to create an appropriate environment for differentiation of immune cells. Studying the cellular expression specificity of receptor and ligand genes reveal the high degree of specificity of these genes that indicate non-random transfer of information between cells in multicellular organisms.