Table 2:

JAK/STAT signaling in the pathogenesis of systemic sclerosis

Cytokines notably involved in the pathogenesis of SSc	JAK associated to their receptor	STAT	Main cellular targets in the context of systemic sclerosis	Main effects
IL-4	JAK1/3	STAT6	-Induces M2 polarization in Macrophages -Fibroblast proliferation	Pro-fibrotic Immuno-modulatory
IL-10	JAK2/TYK2	STAT3	-Could participate in fibrosis through fibroblast activation -Exerts anti-inflammatory effects on B-cell and macrophages	Pro-fibrotic anti-inflammatory
IL-13	JAK1/2/3/TYK2	STAT6	-Induced M2 polarization in Macrophages -Fibroblast proliferation and TGF-β secretion	Pro-fibrotic Immuno-modulatory
IL-6	JAK1/2/TYK2	STAT1/3	-Favor IL-4 receptor expression an M2 polarization -Induce myofibroblast activation	Pro-fibrotic Pro-inflammatory
Interferon α/β (Type 1 IFN)	JAK1/TYK2	STAT1/2/4	-Inhibit the pro-resolving properties of macrophages -participates to endothelial dysfunction	Pro-inflammatory Anti-angiogenic
Interferon γ (Type II IFN)	JAK1/TYK2	STAT1	-Induces M1 polarization in macrophages -Indirect effects on endothelial cells through increased secretion of CXCL10 by M1 -Indirect effects on fibroblasts through increased secretion of IL-6 by M1	Pro-inflammatory Anti-angiogenic