IL-27 inhibits lymphatic endothelial cell proliferation by STAT1-regulated gene expression

OBJECTIVE :: IL-27 belongs to the IL-12 family of cytokines and is recognized for its role in Th cell differentiation and as an inhibitor of tumor angiogenesis. The purpose of this study was to investigate the effect of IL-27 on proliferation of lymphatic endothelial cells to gain insight into the interplay between the immune system and development of the lymphatic system. METHODS : IL-27-stimulated signal transduction in human dermal lymphatic endothelial cells was measured by western blotting and synthesis of CXCL10 and CXCL11 by use of RT-PCR and ELISA. Proliferation was measured using MTT and BrdU kits and the role of STAT1 and chemokines was determined by use of siRNA and recombinant proteins. RESULTS : Stimulation of lymphatic endothelial cell cultures with IL-27 induced JAK dependent phosphorylation of STAT1 and STAT3 and inhibited lymphatic endothelial cell proliferation and migration. Expression of CXCL10 and CXCL11, both STAT1 target genes, was profoundly up-regulated upon IL-27 stimulation, and recombinant CXCL10 and CXCL11 inhibited FGF-2-induced proliferation in vitro. siRNA targeting of STAT1 almost completely abrogated CXCL10 and CXCL11 expression as well as the proliferative effect of IL-27. CONCLUSIONS : IL-27 function as an anti-lymphangiogenic regulator in vitro by up-regulating chemokines and interfering with the mitogenic effect of growth factors through STAT1 activation.Grants from Center for Healthy Ageing (Nordea Fonden), Novo Nordisk Fonden, Carlsberg Fonden, Fonden til Lægevidenskabens Fremme (AP Møller), Harboe Fonden, Psoriasis Fonden, and Købmand M. Kristjan Kjær og Hustru Margrethe Kjær, Født La Cour-Holmes Fond. Remove selectedhttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1549-8719hb2016Immunolog

Winters are changing: snow effects on Arctic and alpine tundra ecosystems

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes and biogeochemical cycling. We also compare studies of natural snow gradients with snow manipulation studies, altering snow depth and duration, to assess time scale difference of these approaches. The number of studies on snow in tundra ecosystems has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. In specific, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by manipulative studies (average 7.9 days advance, 5.5 days delay) were substantially lower than those observed over spatial gradients (mean range of 56 days) or due to interannual variation (mean range of 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates

Winters are changing: snow effects on Arctic and alpine tundra ecosystems

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C+NK cells has remained unclear. Here we found that adaptive NKG2C+NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C+NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C+NK cell populations among HCMV-seropositive people