Table 2.

Role of type I and III IFNs in respiratory and intestinal epithelial cells.

	Lung	Gut
Antiviral functions in epithelial cells	Type III IFNs control viral infection in the upper respiratory tract (25, 109) Both type I and III IFNs control viral infection in the lower respiratory tract (104) Type III IFN acts first and type I IFN acts when infections persist (29)	Type III IFNs act on epithelial cells to control infection (23–25, 71, 95, 96, 98, 99) Type I IFNs act on lamina propria to prevent systemic spread (23, 24, 95, 99) Type III IFNs can control virus infection in epithelial cells in the absence of adaptative immune response (94)
Organ-specific ISGs	Unknown if lung epithelial cells produce ISGs that are not induced in intestinal epithelial cells	Mmp7, Serpinb1a, and Csprs expressed in gut but not in lung following IFNλ2 treatment (84)
Importance of IFN signaling in immune cells	Type III IFNs are needed to reinforce adaptative immune responses (30, 106) Neutrophils depleted of IFNLR were unable to control fungal infections in the lung (108)	Innate lymphoid cells produce IL-22 which synergize with type III IFNs to induce higher levels of ISGs and increase antiviral (rotavirus) protection of murine IECs (97, 117)
Barrier functions of epithelium	Type I IFNs and IFNAR are required to maintain the lung epithelial barrier function following S. pneumoniae infection (110) Chronic type III IFN stimulation of lung epithelial cells leads to loss of barrier function and bacteria infiltration (115, 116)	Type I and III IFNs help to maintain the intestinal epithelial barrier function following Salmonella enterica serovar Typhimurium infection. Type III IFN is more potent in promoting barrier function (111)
Microbiota	Currently unknown if bacteria play a role in shaping interferon responses in the lung	Microbiota promote norovirus persistent infection via modulation of type III IFN signaling (100)