An Alternate STAT6-Independent Pathway Promotes Eosinophil Influx into Blood during Allergic Airway Inflammation

Enhanced eosinophil responses have critical roles in the development of allergic diseases. IL-5 regulates the maturation, migration and survival of eosinophils, and IL-5 and eotaxins mediate the trafficking and activation of eosinophils in inflamed tissues. CD4⁺ Th2 cells are the main producers of IL-5 and other cells such as NK also release this cytokine. Although multiple signalling pathways may be involved, STAT6 critically regulates the differentiation and cytokine production of Th2 cells and the expression of eotaxins. Nevertheless, the mechanisms that mediate different parts of the eosinophilic inflammatory process in different tissues in allergic airway diseases remain unclear. Furthermore, the mechanisms at play may vary depending on the context of inflammation and microenvironment of the involved tissues. We employed a model of allergic airway disease in wild type and STAT6-deficient mice to explore the roles of STAT6 and IL-5 in the development of eosinophilic inflammation in this context. Quantitative PCR and ELISA were used to examine IL-5, eotaxins levels in serum and lungs. Eosinophils in lung, peripheral blood and bone marrow were characterized by morphological properties. CD4⁺ T cell and NK cells were identified by flow cytometry. Antibodies were used to deplete CD4⁺ and NK cells. We showed that STAT6 is indispensible for eosinophilic lung inflammation and the induction of eotaxin-1 and -2 during allergic airway inflammation. In the absence of these chemokines eosinophils are not attracted into lung and accumulate in peripheral blood. We also demonstrate the existence of an alternate STAT6-independent pathway of IL-5 production by CD4⁺ and NK cells that mediates the development of eosinophils in bone marrow and their subsequent movement into the circulation

Expansion of CD4+CD25+ and CD25- T-Bet, GATA-3, Foxp3 and RORγt Cells in Allergic Inflammation, Local Lung Distribution and Chemokine Gene Expression

Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2′-deoxyuridine (BrdU) together with 7-aminoactnomycin (7-AAD). The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet+, GATA-3+, RORγt+ and Foxp3+ cells in CD4+CD25+ and CD4+CD25- T cells, with the greatest expansion of GATA-3+ cells. The majority of CD4+CD25+ T-bet+, GATA-3+, RORγt+ and Foxp3+ cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet+, GATA-3+ and Foxp3+ cells in peribronchial and alveolar tissue, GATA-3+ and Foxp3+ cells in perivascular tissue, and RORγt+ cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu

GM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis

Dysregulated hematopoiesis occurs in several chronic inflammatory diseases, but it remains unclear how hematopoietic stem cells (HSCs) in the bone marrow (BM) sense peripheral inflammation and contribute to tissue damage in arthritis. Here, we show the HSC gene expression program is biased toward myelopoiesis and differentiation skewed toward granulocyte-monocyte progenitors (GMP) during joint and intestinal inflammation in experimental spondyloarthritis (SpA). GM-CSF-receptor is increased on HSCs and multipotent progenitors, favoring a striking increase in myelopoiesis at the earliest hematopoietic stages. GMP accumulate in the BM in SpA and, unexpectedly, at extramedullary sites: in the inflamed joints and spleen. Furthermore, we show that GM-CSF promotes extramedullary myelopoiesis, tissue-toxic neutrophil accumulation in target organs, and GM-CSF prophylactic or therapeutic blockade substantially decreases SpA severity. Surprisingly, besides CD4+ T cells and innate lymphoid cells, mast cells are a source of GM-CSF in this model, and its pathogenic production is promoted by the alarmin IL-33

Acoustic telemetry reveals strong spatial preferences and mixing during successive spawning periods in a partially migratory common bream population

Partial migration, whereby a population comprises multiple behavioural phenotypes that each have varying tendencies to migrate, is common among many animals. Determining the mechanisms by which these phenotypes are maintained is important for understanding their roles in population structure and stability. The aim here was to test for the temporal and spatial consistency of migratory phenotypes in a common bream Abramis brama (‘bream’) population, and then determine their social preferences and extent of mixing across three successive annual spawning periods. The study applied passive acoustic telemetry to track the movements of bream in the River Bure system of the Norfolk Broads, a lowland wetland comprising highly connected riverine and lacustrine habitats. Analyses revealed that individual migratory phenotype was highly consistent across the three years, but this was not predicted by fish sex or length at tagging. During the annual spawning periods, network analyses identified off-channel areas visited by both resident and migrant fish that, in non-spawning periods, were relatively independent in their space use. Within these sites, the co-occurrence of bream was non-random, with individuals forming more preferred and avoided associations than expected by chance. These associations were not strongly predicted by similarity in fish length, sex or behavioural phenotype, indicating that the resident and migrant phenotypes mixed during their annual spawning periods. The results suggested these different phenotypes, with spatially distinct resource use in non-spawning periods, comprised a single metapopulation, with this having important implications for the management of this wetland resource

Effective monitoring of freshwater fish

Freshwater ecosystems constitute only a small fraction of the planet’s water resources, yet support much of its diversity, with freshwater fish accounting for more species than birds, mammals, amphibians, or reptiles. Fresh waters are, however, particularly vulnerable to anthropogenic impacts, including habitat loss, climate and land use change, nutrient enrichment, and biological invasions. This environmental degradation, combined with unprecedented rates of biodiversity change, highlights the importance of robust and replicable programmes to monitor freshwater fish assemblages. Such monitoring programmes can have diverse aims, including confirming the presence of a single species (e.g. early detection of alien species), tracking changes in the abundance of threatened species, or documenting long-term temporal changes in entire communities. Irrespective of their motivation, monitoring programmes are only fit for purpose if they have clearly articulated aims and collect data that can meet those aims. This review, therefore, highlights the importance of identifying the key aims in monitoring programmes, and outlines the different methods of sampling freshwater fish that can be used to meet these aims. We emphasise that investigators must address issues around sampling design, statistical power, species’ detectability, taxonomy, and ethics in their monitoring programmes. Additionally, programmes must ensure that high-quality monitoring data are properly curated and deposited in repositories that will endure. Through fostering improved practice in freshwater fish monitoring, this review aims to help programmes improve understanding of the processes that shape the Earth's freshwater ecosystems, and help protect these systems in face of rapid environmental change

Susceptibility of European freshwater fish to climate change: Species profiling based on life-history and environmental characteristics

Climate change is expected to strongly affect freshwater fish communities. Combined with other anthropogenic drivers, the impacts may alter species spatio-temporal distributions and contribute to population declines and local extinctions. To provide timely management and conservation of fishes, it is relevant to identify species that will be most impacted by climate change and those that will be resilient. Species traits are considered a promising source of information on characteristics that influence resilience to various environmental conditions and impacts. To this end, we collated life-history traits and climatic niches of 443 European freshwater fish species and compared those identified as susceptible to climate change to those that are considered to be resilient. Significant differences were observed between the two groups in their distribution, life history, and climatic niche, with climate-change-susceptible species being distributed within the Mediterranean region, and being characterized by greater threat levels, lesser commercial relevance, lower vulnerability to fishing, smaller body and range size, and warmer thermal envelopes. Based on our results, we establish a list of species of highest priority for further research and monitoring regarding climate-change susceptibility within Europe. The presented approach represents a promising tool to efficiently assess large groups of species regarding their susceptibility to climate change and other threats, and to identify research and management priorities.Preprint: [https://doi.org/10.1101/355875