Interferon-Lambda: A Potent Regulator of Intestinal Viral Infections

Lee, Sanghyun; Baldridge, Megan T.

While the antiviral programs induced by type I and type III IFNs exhibit substantial overlap (20) (21) (22) (Figure 1) , a critical difference between the two is the cell types they affect secondary to receptor expression. The IFN-λ receptor consists of IFNLR1 and IL10Rβ. While the receptor for type I IFNs, IFNAR1, is expressed broadly on the majority of cell types, IFNLR1 exhibits a much more restricted pattern of expression (23) . In the intestine, IFNLR1 is expressed preferentially on IECs, allowing for a compartmentalized response to viruses infecting at this mucosal surface (24, 25) . While IFNLR1 expression has also been reported on NK cells, T cells, B cells, and pDCs (26) (27) (28) (29) (30) , no role has been found for these cells in IFN-λ-mediated antiviral responses. Type I IFNs, on the other hand, are critical for preventing a virus from moving past this initial epithelial barrier into systemic tissues (24, 25, 31) . The host may benefit by inducing specific and local barrier defenses at a site commonly exposed to pathogens via IFN-λ signaling, and thus avoid potentially detrimental systemic inflammatory responses by type I IFNs. Many autoimmune diseases, as well as the congenital interferonopathies, are secondary to excessive type I IFN activity (32, 33) .