The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of ...inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.
There are a multitude of biodiversity informatics projects, datasets, databases and initiatives at the global level, and many more at regional, national, and sometimes local levels. In such a complex ...landscape, it can be unclear how different elements relate to each other. Based on a high-level review of global and European-level elements, we present a map of the biodiversity informatics landscape. This is a first attempt at identifying key datasets/databases and data services, and mapping them in a way that can be used to identify the links, gaps and redundancies in the landscape. While the map is predominantly focused on elements with a global scope, the sub-global focus at the European-level was incorporated in the map in order to demonstrate how a regional network such as the European Biodiversity Observation Network (EU BON) can usefully contribute to connecting some of the nodes within the landscape. We identify 74 elements, and find that the informatics landscape is complex in terms of the characteristics and diversity of these elements, and that there is high variability in their level of connectedness. Overall, the landscape is highly connected, with one element boasting 28 connections. The average "degrees of separation" between elements is low, and the landscape is deemed relatively robust to failures since there is no single point that information flows through. Examples of possible effort duplication are presented, and the inclusion of five policy-level elements in the map helps illustrate how informatics products can contribute to global processes that define and direct political targets. Beyond simply describing the existing landscape, this map will support a better understanding of the landscape’s current structure and functioning, enabling responsible institutions to establish or strengthen collaborations, work towards avoiding effort duplication, and facilitate access to the biodiversity data, information and knowledge required to support effective decision-making, in the context of comparatively limited funding for biodiversity knowledge and conservation. To support this, we provide the input matrix and code that created this map as supplementary materials, so that readers can more closely examine the links in the landscape, and edit the map to suit their own purposes.
PDF
