Environmental factor and inflammation-driven alteration of the total peripheral T-cell compartment in granulomatosis with polyangiitis.

Autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. Autoantibody production and an imbalance of effector and regulatory T-cells are hallmarks of autoimmune dysregulation. While expansion of circulating effector memory T-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral T-cell compartment have remained poorly understood so far. In granulomatosis with polyangiitis (GPA), a prototypical autoimmune disorder of unknown aetiology, we performed for the first time a combined approach using phenotyping, transcriptome and functional analyses of T-cell populations to evaluate triggers of memory T-cell expansion. In more detail, we found increased percentages of circulating CD4+CD28-, CD8+CD28- and CD4+CD161+ single-positive and CD4+CD8+ double-positive T-cells in GPA. Transcriptomic profiling of sorted T-cell populations showed major differences between GPA and healthy controls reflecting antigen- (bacteria, viruses, fungi) and cytokine-driven impact on T-cell populations in GPA. Concomitant cytomegalovirus (CMV) and Epstein-Barr virus (EBV) - positivity was associated with a significant increase in the percentage of CD28- T-cells in GPA-patients compared to sole CMV- or EBV-positivity or CMV- and EBV-negativity. T-cells specific for other viruses (influenza A virus, metapneumovirus, respiratory syncytial virus) and the autoantigen proteinase 3 (PR3) were infrequently detected in GPA. Antigen-specific T-cells were not specifically enriched in any of the T-cell subsets. Altogether, on a genetic and cellular basis, here we show that alterations of the peripheral T-cell compartment are driven by inflammation and various environmental factors including concomitant CMV and EBV infection. Our study provides novel insights into mechanisms driving autoimmune disease and on potential therapeutic targets.

Global acceleration in rates of vegetation change over the past 18,000 years.

Global vegetation over the past 18,000 years has been transformed first by the climate changes that accompanied the last deglaciation and again by increasing human pressures; however, the magnitude and patterns of rates of vegetation change are poorly understood globally. Using a compilation of 1181 fossil pollen sequences and newly developed statistical methods, we detect a worldwide acceleration in the rates of vegetation compositional change beginning between 4.6 and 2.9 thousand years ago that is globally unprecedented over the past 18,000 years in both magnitude and extent. Late Holocene rates of change equal or exceed the deglacial rates for all continents, which suggests that the scale of human effects on terrestrial ecosystems exceeds even the climate-driven transformations of the last deglaciation. The acceleration of biodiversity change demonstrated in ecological datasets from the past century began millennia ago.

Postglacial change of the floristic diversity gradient in Europe.

Climate warming is expected to cause a poleward spread of species, resulting in increased richness at mid to high latitudes and weakening the latitudinal diversity gradient. We used pollen data to test if such a change in the latitudinal diversity gradient occurred during the last major poleward shift of plant species in Europe following the end of the last glacial period. In contrast to expectations, the slope of the gradient strengthened during the Holocene. The increase in temperatures around 10 ka ago reduced diversity at mid to high latitude sites due to the gradual closure of forests. Deforestation and the introduction of agriculture during the last 5 ky had a greater impact on richness in central Europe than the earlier climate warming. These results do not support the current view that global warming alone will lead to a loss in biodiversity, and demonstrate that non-climatic human impacts on the latitudinal diversity gradient is of a greater magnitude than climate change.

Exploring holocene changes in palynological richness in northern Europe--did postglacial immigration matter?

In mid to high latitudes glacial and interglacial cycles have repeatedly changed the area available for plant growth. The speed at which plants are able to colonize areas at the onset of an interglacial is hypothesized to limit their distribution ranges even today (migrational lag). If the spread of plants would have been generally slow then plant diversity in previously glaciated areas would be expected to increase over time. We explore this hypothesis using results from six palynological investigations from two previously glaciated regions: central Sweden and north-eastern Germany. Rarefaction, slope of rank order abundance, and taxa accumulation plots were used to evaluate richness and evenness in pollen data in an attempt to separate richness from evenness. These analyses show little change in palynological richness for the northern sites throughout the Holocene. In contrast, the southern sites show an increase in richness and evenness during the early Holocene; this may be explained by the different initial conditions at the onset of the Holocene. A strong rise in palynological richness around 6000 and 1000 years ago at the southern sites can be attributed to the regional initiation of agriculture and major opening of the forest, respectively. For the northern sites there is no evidence for increased taxonomic diversity through time that could be due to delayed immigration of species.