Table 1.

Similarities and differences of type I and III IFNs.

	Type I IFN	Type III IFN
IFN production	Produced downstream TLR3, TLR4 (endosomes), RLRs, STING (32–35) Produced by MAVS located on mitochondria (38, 39)	Produced downstream TLR3, TLR4 (endosomes), RLRs, STING (32–35) Produced by MAVS located on both mitochondria and peroxisomes (38, 39)
Receptor distribution	Receptor expressed by all cells in the body (10)	IFNLR receptor chain is only expressed in epithelial cells and in some immune cells (DCs, pDCs, NK cells and neutrophils) (23–31)
JAK/STAT signaling	Requires JAK1 (JAK2 independent) (30, 39, 55, 57–59, 64, 72) Signaling is TYK2 dependent (52–55)	Requires JAK1 and JAK2 (30, 39, 72) Signaling is TYK2 independent (61–63)
Other pathways	Negatively regulated by IFNLR (82)	Positively regulated by IFNAR (82) Requires MAPKs for its antiviral activity (71)
Magnitude and kinetics of ISG induction	High magnitude of ISG induction (46–48, 83, 85) Fast induction and fast decrease in ISG expression (46–48, 83, 85)	Low magnitude of ISG induction (46–48, 83, 85) Slow but sustained induction of ISGs (46–48, 83, 85)
Negative regulators	USP18 downregulates IFN-mediated signaling (77, 79, 81) SOCS1 and 3 downregulate IFN-mediated signaling (74–76)	SOCS1 downregulates signaling is some tissues (76)
IFN-specific ISGS	IRF1 (85–87)	Mmp7, Serpinb1a, and Csprs (84)