The spectrum of macrophages phenotypes could be determined by PPInetwork and transcription f actor enrichment analysis

Macrophages, the key cells of innate immune system play a critical role in tissue hemostasis (۱). Various reports have determined that macrophages could acquire different phenotypes from proinflamatory-M۱ to anti-inflammatory M۲, M۲-like sub-groups and other uncharacterized groups (۲). It is shown that different stimulus combinations in the microenvironment could affect the function of macrophages (۳). Understanding the molecular circuits that control switching behavior of macrophages is of great importance. In a recent mathematical approach, we determined that macrophages acquire ۹ stable phenotypes in response to input stimulus IL۴, IFNγ and LPS (۴). Also we found that STAT۱, STAT۶, and NFκB are key transcription factors in macrophage fate-determination (figure ۱). To check for importance of transcription factors in macrophages transcriptional reprograming we performed a top-down systems biology approach.

Keywords:

Macrophages polarization , PPI-network analysis , Enrichment Analysis