Abstract
Interferon lambdas (IFNλs) are recently discovered cytokines acting not only at the first line of defense against viral infections but also at the mucosal barriers. In fact, a peculiar feature of the IFNλ system is the restricted expression of the functional IFNλR, which is known to be limited to epithelial cells and discrete leukocyte subsets, including the plasmacytoid dendritic cells (pDCs). In the latter case, current data, discussed in this minireview, indicate that IFNλs positively regulate various pDC functions, including pDC expression of interferon-dependent gene (ISG) mRNAs, production of cytokines, survival, and phenotype. Although the knowledge of the effects on pDCs by IFNλs is still incomplete, we speculate that the peculiar pDC responsiveness to IFNλs provide unique advantages for these innate immune cells, not only for viral infections but also during autoimmune disorders and/or tumors, in which pDC involvement and activation variably contribute to their pathogenesis.
Highlights
Human dendritic cells (DCs) in the blood typically include the myeloid DCs, enlisting the BDCA1+/CD1c+ and BDCA3+/CD141+ DCs, as well as the plasmacytoid DCs [1]
As synthetically outlined in this minireview, current data suggest that IFNλ is able to regulate plasmacytoid DCs (pDCs) functions at various levels, including the production of IFNα, CXCL10, and TNFα
Because IFNα has been shown to increase the production of IFNλ by CD141+ DCs in response to hepatitis C virus (HCV)-infected hepatoma cells or poly-I:C [30], data testify for potential cross talk between pDCs and CD141+ DCs via the two IFN systems
Summary
A peculiar feature of the IFNλ system is the restricted expression of the functional IFNλR, which is known to be limited to epithelial cells and discrete leukocyte subsets, including the plasmacytoid dendritic cells (pDCs). In the latter case, current data, discussed in this minireview, indicate that IFNλs positively regulate various pDC functions, including pDC expression of interferon-dependent gene (ISG) mRNAs, production of cytokines, survival, and phenotype. The knowledge of the effects on pDCs by IFNλs is still incomplete, we speculate that the peculiar pDC responsiveness to IFNλs provide unique advantages for these innate immune cells, for viral infections and during autoimmune disorders and/or tumors, in which pDC involvement and activation variably contribute to their pathogenesis
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