IFN-Lambda (IFN-λ) Is Expressed in a Tissue-Dependent Fashion and Primarily Acts on Epithelial Cells In Vivo

Abstract

Interferons (IFN) exert antiviral, immunomodulatory and cytostatic activities. IFN-α/β (type I IFN) and IFN-λ (type III IFN) bind distinct receptors, but regulate similar sets of genes and exhibit strikingly similar biological activities. We analyzed to what extent the IFN-α/β and IFN-λ systems overlap in vivo in terms of expression and response. We observed a certain degree of tissue specificity in the production of IFN-λ. In the brain, IFN-α/β was readily produced after infection with various RNA viruses, whereas expression of IFN-λ was low in this organ. In the liver, virus infection induced the expression of both IFN-α/β and IFN-λ genes. Plasmid electrotransfer-mediated in vivo expression of individual IFN genes allowed the tissue and cell specificities of the responses to systemic IFN-α/β and IFN-λ to be compared. The response to IFN-λ correlated with expression of the α subunit of the IFN-λ receptor (IL-28Rα). The IFN-λ response was prominent in the stomach, intestine and lungs, but very low in the central nervous system and spleen. At the cellular level, the response to IFN-λ in kidney and brain was restricted to epithelial cells. In contrast, the response to IFN-α/β was observed in various cell types in these organs, and was most prominent in endothelial cells. Thus, the IFN-λ system probably evolved to specifically protect epithelia. IFN-λ might contribute to the prevention of viral invasion through skin and mucosal surfaces.

The role of transposable elements in the regulation of IFN-λ1 gene expression

“…In contrast to almost ubiquitous expression of type I IFNs and their receptor, which results in a widespread protective antiviral immunity, IFN-R1 is expressed primarily on epithelial and plasmacytoid dendritic cells (pDCs), contributing to the prevention of viral invasion through skin and mucosal surfaces (13). DCs are also the major producers of IFN-s in response to virus induction or Toll-like receptor (TLR) signaling (14).…”

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…The IFN-k response was prominent in the stomach, intestine, and lungs, and was mainly restricted to epithelial cells. In contrast, the response to IFN-a/b was more ubiquitous and was observed in various cell types [106]. These results raised the hypothesis that the IFN-k system probably evolved to specifically protect epithelia.…”

“…The tissue and cell specificities of the responses to systemic IFN-a/b and IFN-k have been recently compared by the group of Michiels [106]. The response to IFN-k correlated with expression of IFN-kR1.…”

Interfering with Immunity: Detrimental Role of Type I IFNs during Infection

“…However, the magnitude of STAT activation and subsequent biological activities induced by type I IFNs are often greater than those induced by type III IFNs (19). In addition, unlike the type I IFNR, which is expressed almost ubiquitously on all cells, IFNLR1 is expressed predominantly on epithelial cells (20). Therefore, the biological role of type III IFNs is believed to be much more restricted than that of type I IFNs.…”