About this Research Topic
Interferons (IFNs) are produced as a result of the intricate molecular cascade that is triggered during inflammatory processes. They play critical roles in regulating proliferation, differentiation, survival and effector functions of immune and non-immune cell types. IFNs are divided into three classes: type I IFNs (comprised of IFN-αs, -β and others), type II IFNs (IFN-γ) and a more recently discovered class called type III IFNs or IFN-λ1-3 (also known as IL29, IL28A-B) and IFN-λ4 (only IFN-λ2 and 3 are present in mice). IFN-λs are recognized by the IFN-λ receptor (IFNLR), which is a heterodimer comprising IL-10RB (shared by the IL-10 cytokine family) and IFNLR1 (that confers recognition specificity for IFN-λs) chains.
The IFNLR is distinct from the ubiquitous receptors for type I and II IFNs in that it has a very restricted pattern of expression, being primarily by epithelial cells and by a limited array of immune cells. The IFNLR was originally thought to signal through the same JAK/STAT members also used by the receptor for IFN-α/β - this is why the IFN-λs, when initially discovered, were believed to have functions that were redundant with those of IFN-α/β. Recently, however, a series of elegant studies demonstrated that IFN-λs have unique functions relative to IFN-α/β in terms of maintaining stromal cell resistance and homeostasis in response to viral infections or in the context of inflammation-driven pathologies. Nevertheless, how cells that have the potential to respond to IFN-α/β also require signaling by IFN-λs to efficiently react to different inflammatory challenges has not yet been settled. Recent work has also shown that type I and III IFNs are not co-regulated as once thought, and that IFN-λs can be induced via distinct signaling pathways.
This Research Topic discusses the regulatory mechanisms that lead to type III IFN expression, and aims to dissect the non-redundant roles played by IFN-λs by non-immune and immune cells in the context of microbial and non-microbial driven inflammatory processes, with special emphasis on the peculiar responses associated with the IFN-λ signaling cascade.
The IFNLR is distinct from the ubiquitous receptors for type I and II IFNs in that it has a very restricted pattern of expression, being primarily by epithelial cells and by a limited array of immune cells. The IFNLR was originally thought to signal through the same JAK/STAT members also used by the receptor for IFN-α/β - this is why the IFN-λs, when initially discovered, were believed to have functions that were redundant with those of IFN-α/β. Recently, however, a series of elegant studies demonstrated that IFN-λs have unique functions relative to IFN-α/β in terms of maintaining stromal cell resistance and homeostasis in response to viral infections or in the context of inflammation-driven pathologies. Nevertheless, how cells that have the potential to respond to IFN-α/β also require signaling by IFN-λs to efficiently react to different inflammatory challenges has not yet been settled. Recent work has also shown that type I and III IFNs are not co-regulated as once thought, and that IFN-λs can be induced via distinct signaling pathways.
This Research Topic discusses the regulatory mechanisms that lead to type III IFN expression, and aims to dissect the non-redundant roles played by IFN-λs by non-immune and immune cells in the context of microbial and non-microbial driven inflammatory processes, with special emphasis on the peculiar responses associated with the IFN-λ signaling cascade.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
