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. 2021 Jun 9;22(12):6211. doi: 10.3390/ijms22126211

Figure 1.

Figure 1

JAK/STAT activation and downstream signaling pathways in ILDs. (A) IL-4 binds to the type-I IL-4 receptor, constituted by the IL-4 receptor α chain (IL-4Rα) and the gamma chain (γc). Additionally, both IL-4 and IL-13 bind to the type II receptor made up of IL-4Rα/IL-13Rα1. Stimulation of these receptors activates IL-4Rα and associated JAK1 to phosphorylate STAT6 monomers, which then homodimerize and translocate to the nucleus when it activates fibrotic responses. (B) IL-6 and IL11 activate the receptor gp130. This receptor has shown binding to JAK1, JAK2, and TYK2 in other diseases; however, in ILDs, is not elucidated, which JAK induces the phosphorylation of STAT3. The same happens after gp130 stimulation by IL-31, which leads to STAT1 activation. Then, both STAT3 and STAT1 travel dimerized to the nucleus. (C) Non-canonical activation of TGF-β1 signaling pathway starts with its binding to the TGF-β1 receptor, and then the phosphorylation of JAK2 occurs, leading to STAT3 activation and homodimerization. (D) Indirect evidence of JAK/STAT pathway activation by growth factors. Here, there are represented the different JAKs and STATS found activated after stimulation of each receptor with epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) in other diseases different to ILD. The image was created with BioRender.