Fig. 3.

Macrophage polarization – JAK/STAT pathway.

Binding of IFNγ, LPS or IL-4/13 to their corresponding surface receptors triggers activation of JAKs (Janus Kinases) which induces activation of STATs (Signal transducer and activators of transcription) and transcription of M1and M2 genes. These genes are also transcribed by the differential activation of Akt1/2 via PI3K or PIP3. Binding of IFNγ to IFNγR1/2 activates JAK1/2, which in turn, activates STAT1/3. STAT1/3 induces activation of NF-κβ. Binding of LPS to TLR4 also activates NF-κβ via adapter proteins MyD88 (Myeloid differentiation primary response 88)/TRIF (TIR-domain containing adapter-inducing interferon-β). KLF4 inhibits the activity of NF-κβ. SOCS3 (suppressor of cytokine signalling 3) negatively regulates the cytokine signalling by binding to JAK2 kinase and inhibiting its activity. Binding of IL-4 to its receptor activates JAK1/2/3 kinases or PI3 kinases. Activated JAKs trigger activation of PPARγ/δ (Peroxisome proliferator-activated receptor gamma) via STAT6, which in turn, activates M2 genes. Akt1 activation promotes activation of M1 genes and Akt2 activation promotes activation of M2 genes.