Figure 5.

Transcriptional mechanisms of macrophage polarization in T2D. M1 macrophages polarize in response to TLR2 or TLR4 ligation, downstream signaling is dependent of two adaptor complexes: Mal/TIRAP–MyD88 (TLR2 and TLR4) and TRAM–TRIF (TLR4). IRAK and TRAF signaling then dictate which transcriptional programmes are engaged, IRF3 IRF5, AP1, and NFκB have been shown to induce inflammatory polarization in T2D. M2 macrophages polarize downstream of cytokine and fatty acid receptor stimulation (also possible through other molecules such as TREM2). Intermediate signaling is largely through STATs and nuclear receptors (LXR and PPAR). STATs act as transcription factors or activate IRF4, whereas nuclear receptors act through transrepression of M1 transcription factors (M1 TF).