Interferon-λ Receptor Expression: Novel Reporter Mouse Reveals Within- and Cross-Tissue Heterogeneity.

Interferon-lambda (IFN-lambda) plays an important role in mucosal immunity, but reliable information regarding the expression of the IFN-lambda receptor in individual cells is still missing. One reason for this knowledge gap is the lack of antibodies that specifically recognize the unique IFNLR1 subunit of the dimeric IFN-lambda receptor complex. In this study, we investigated whether a reporter mouse carrying a bacterial beta-galactosidase gene inserted into theIfnlr1locus could be used to visualize IFN-lambda receptor-expressing cells in whole organs. First we confirmed that insertion of the reporter cassette inactivated theIfnlr1gene, and that gene function could be restored by removing the beta-galactosidase insert by site-specific recombination. When whole tissues were analyzed, prominent beta-galactosidase activity was confined to the intestinal tract of reporter mice. However, only the snout expressed beta-galactosidase at levels high enough for reliable detection in whole tissue extracts. Interestingly, individual epithelial cells in the upper airways expressed beta-galactosidase activity to variable degrees as determined by flow cytometry and histology, suggesting a remarkable heterogeneity in IFNLR1 expression levels. Taken together, our results demonstrate a surprisingly strong within- and cross-tissue heterogeneity of IFNLR1 expression that may have physiological implications.