Table 2.

JAK-STAT signaling pathways affecting intestinal permeability. (JAK: Janus Kinase, STAT: Signal Transducer and Activator of Transcription, IL-22: Interleukin 22, IFN-γ: Interferon gamma, IL-6: Interleukin 6, IL-13: Interleukin 13, JAM-A: Junctional Adhesion Molecule-A, ZO-1: Zonula Occludens-1, TEER: Transepithelial electrical resistance, FD4: 4-kilodalton fluorescein isothiocyanate-dextran, SOCS: Suppressor of Cytokine Signaling, siRNA: Small interfering ribonucleic acid).

JAK-STATs	Activators in IBD	Effect on TJ Proteins	Effect on Permeability	JAK/STAT Inhibitors	References
STAT1 and STAT3	IL-22	Increased claudin-2 expression	Increased paracellular permeability to ionic solutes; Reduced TEER	JAK Inhibitor 1 and AZD1480 (Inhibited the STAT3-dependent gene, SOCS3)	[41]
JAK1-STAT1/STAT3	IFN-γ	Increased claudin-2 expression	Increased paracellular permeability; Reduced TEER, Increased FD4 permeability	Tofacitinib	[9]
STAT3	IL-6	Increases claudin-2 expression	Increases paracellular permeability to ionic solutes; Reduced TEER	AG490, STAT3 siRNA	[35,43]
Undetermined	Presumably IFN-γ	Decreased JAM-A expression; Possible redistribution of JAM-A	Increased paracellular permeability to macromolecules; Presumably reduces TEER and increases FD4 permeability	Tofacitinib	[8]
Undetermined	IFN-γ	Decreased occludin expression; Redistribution of occludin	Increased paracellular permeability to larger macromolecules	Tofacitinib	[8,9]
JAK1/JAK2	IL-13, IFN-γ	Downregulation of tricellulin; Redistribution of tricellulin	Increased uptake of macromolecules through the paracellular space	Baricitinib, Tofacitinib	[8,9,66]
STAT3 and JAK2	Leptin	Downregulation of angulin-1	Tricellulin localization is altered; Increased intestinal permeability	Stattic, WP1006, and partially by AG490	[66,67,68]
Undetermined	IFN-γ	Downregulation and redistribution of ZO-1	Increased paracellular permeability to macromolecules	Tofacitinib	[8,9]