A preliminary phylogeographic study of Flavopunctelia and Punctelia inferred from rDNA ITS-sequences

A preliminary phylogeny of the genera Flavopunctelia and Punctelia is presented. Genus and species delimitations have been investigated using ITS rDNA-sequencing of populations from different continents. Current genus delimitations of Flavopunctelia, Punctelia and Parmelia are confirmed and the species status of recently resurrected Punctelia ulophylla is confirmed. The status of three cryptic species, Flavopunctelia soredica, Punctelia perreticulata and P. stictica is discussed. Flavopunctelia borrerioides and Punctelia perreticulata are reported from China for the first time.Esitatakse perekondade Flavopunctelia ja Punctelia esialgne fülogeneesi rekonstruktsioon. Perekondade ja liikide eraldamist on uuritud erinevatelt kontinentidelt pärinevate populatsioonide ITS rDNA sekventside alusel. Senine perekondade Flavopunctelia, Punctelia ja Parmelia piiritlemine on leidnud kinnitust, samuti liigi Punctelia ulophylla staatus. Arutletakse kolme krüptilise liigi, Flavopunctelia soredica, Punctelia perreticulata ja P. stictica staatuse üle. Teatatakse liikide Flavopunctelia borrerioides ja Punctelia perreticulata esmasleidudest HiinasFil: Thell, Arne. Lund University; SueciaFil: Herber, B.. Universitat Hamburg; AlemaniaFil: Aptroot, A.. Centraalbureau voor Schimmelcultures; Países BajosFil: Adler, Monica Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Micología y Botánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Micología y Botánica; ArgentinaFil: Feuerer, T.. Universitat Hamburg; AlemaniaFil: Kärnefelt, Ingvar. Lund University; Sueci

Phylogeny of the cetrarioid core (Parmeliaceae) based on five genetic markers

Fourteen genera belong to a monophyletic core of cetrarioid lichens, Ahtiana, Allocetraria, Arctocetraria, Cetraria, Cetrariella, Cetreliopsis, Flavocetraria, Kaernefeltia, Masonhalea, Nephromopsis, Tuckermanella, Tuckermannopsis, Usnocetraria and Vulpicida. A total of 71 samples representing 65 species (of 90 worldwide) and all type species of the genera are included in phylogentic analyses based on a complete ITS matrix and incomplete sets of group I intron, -tubulin, GAPDH and mtSSU sequences. Eleven of the species included in the study are analysed phylogenetically for the first time, and of the 178 sequences, 67 are newly constructed. Two phylogenetic trees, one based solely on the complete ITS-matrix and a second based on total information, are similar, but not entirely identical. About half of the species are gathered in a strongly supported clade composed of the genera Allocetraria, Cetraria s. str., Cetrariella and Vulpicida. Arctocetraria, Cetreliopsis, Kaernefeltia and Tuckermanella are monophyletic genera, whereas Cetraria, Flavocetraria and Tuckermannopsis are polyphyletic. The taxonomy in current use is compared with the phylogenetic results, and future, probable or potential adjustments to the phylogeny are discussed. The single non-DNA character with a strong correlation to phylogeny based on DNA-sequences is conidial shape. The secondary chemistry of the poorly known species Cetraria annae is analyzed for the first time; the cortex contains usnic acid and atranorin, whereas isonephrosterinic, nephrosterinic, lichesterinic, protolichesterinic and squamatic acids occur in the medulla. Notes on the anatomy of Cetraria annae and Flavocetraria minuscula are also provided

Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment

Some mature natural killer (NK) cells cannot be inhibited by major histocompatibility complex (MHC) I molecules, either because they lack corresponding inhibitory receptors or because the host lacks the corresponding MHC I ligands for the receptors. Such NK cells nevertheless remain self-tolerant and exhibit a generalized hyporesponsiveness to stimulation through activating receptors. To address whether NK cell responsiveness is set only during the NK cell differentiation process, we transferred mature NK cells from wild-type (WT) to MHC I–deficient hosts or vice versa. Remarkably, mature responsive NK cells from WT mice became hyporesponsive after transfer to MHC I–deficient mice, whereas mature hyporesponsive NK cells from MHC I–deficient mice became responsive after transfer to WT mice. Altered responsiveness was evident among mature NK cells that had not divided in the recipient animals, indicating that the cells were mature before transfer and that alterations in activity did not require cell division. Furthermore, the percentages of NK cells expressing KLRG1, CD11b, CD27, and Ly49 receptors specific for H-2b were not markedly altered after transfer. Thus, the functional activity of mature NK cells can be reset when the cells are exposed to a changed MHC environment. These findings have important implications for how NK cell functions may be curtailed or enhanced in the context of disease

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

NK Cells Are Not Required for Spontaneous Autoimmune Diabetes in NOD Mice

NK cells have been shown to either promote or protect from autoimmune diseases. Several studies have examined the role of receptors preferentially expressed by NK cells in the spontaneous disease of NOD mice or the direct role of NK cells in acute induced disease models of diabetes. Yet, the role of NK cells in spontaneous diabetes has not been directly addressed. Here, we used the NOD.NK1.1 congenic mouse model to examine the role of NK cells in spontaneous diabetes. Significant numbers of NK cells were only seen in the pancreas of mice with disease. Pancreatic NK cells displayed an activated surface phenotype and proliferated more than NK cells from other tissues in the diseased mice. Nonetheless, depletion of NK cells had no effect on dendritic cell maturation or T cell proliferation. In spontaneous disease, the deletion of NK cells had no significant impact on disease onset. NK cells were also not required to promote disease induced by adoptively transferred pathogenic CD4+ T cells. Thus, NK cells are not required for spontaneous autoimmune diabetes in NOD mice

MicroRNA 10a Marks Regulatory T Cells

MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD) mice with a genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a expression than C57BL/6J autoimmune resistant mice. Inhibition of miR-10a expression in vitro leads to reduced FoxP3 expression levels and miR-10a expression is lower in unstable “exFoxP3” T cells. Unstable in vitro TGF-ß-induced, iTregs do not express miR-10a unless cultured in the presence of retinoic acid (RA) which has been associated with increased stability of iTreg, suggesting that miR-10a might play a role in stabilizing Treg. However, genetic ablation of miR-10a neither affected the number and phenotype of natural Treg nor the capacity of conventional T cells to induce FoxP3 in response to TGFβ, RA, or a combination of the two. Thus, miR-10a is selectively expressed in Treg but inhibition by antagomiRs or genetic ablation resulted in discordant effects on FoxP3

TNF signalling drives expansion of bone marrow CD4+ T cells responsible for HSC exhaustion in experimental visceral leishmaniasis

Visceral leishmaniasis is associated with significant changes in hematological function but the mechanisms underlying these changes are largely unknown. In contrast to naïve mice, where most long-term hematopoietic stem cells (LT-HSCs; LSK CD150+ CD34- CD48- cells) in bone marrow (BM) are quiescent, we found that during Leishmania donovani infection most LT-HSCs had entered cell cycle. Loss of quiescence correlated with a reduced self-renewal capacity and functional exhaustion, as measured by serial transfer. Quiescent LT-HSCs were maintained in infected RAG2 KO mice, but lost following adoptive transfer of IFNγ-sufficient but not IFNγ-deficient CD4+ T cells. Using mixed BM chimeras, we established that IFNγ and TNF signalling pathways converge at the level of CD4+ T cells. Critically, intrinsic TNF signalling is required for the expansion and/or differentiation of pathogenic IFNγ+CD4+ T cells that promote the irreversible loss of BM function. These finding provide new insights into the pathogenic potential of CD4+ T cells that target hematopoietic function in leishmaniasis and perhaps other infectious diseases where TNF expression and BM dysfunction also occur simultaneously

Scavenger Receptor CD36 Expression Contributes to Adipose Tissue Inflammation and Cell Death in Diet-Induced Obesity

The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.Compared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS). Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects.CD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes

Adora2b Adenosine Receptor Engagement Enhances Regulatory T Cell Abundance during Endotoxin-Induced Pulmonary Inflammation

Anti-inflammatory signals play an essential role in constraining the magnitude of an inflammatory response. Extracellular adenosine is a critical tissue-protective factor, limiting the extent of inflammation. Given the potent anti-inflammatory effects of extracellular adenosine, we sought to investigate how extracellular adenosine regulates T cell activation and differentiation. Adenosine receptor activation by a pan adenosine-receptor agonist enhanced the abundance of murine regulatory T cells (Tregs), a cell type critical in constraining inflammation. Gene expression studies in both naïve CD4 T cells and Tregs revealed that these cells expressed multiple adenosine receptors. Based on recent studies implicating the Adora2b in endogenous anti-inflammatory responses during acute inflammation, we used a pharmacologic approach to specifically activate Adora2b. Indeed, these studies revealed robust enhancement of Treg differentiation in wild-type mice, but not in Adora2b−/− T cells. Finally, when we subjected Adora2b-deficient mice to endotoxin-induced pulmonary inflammation, we found that these mice experienced more severe inflammation, characterized by increased cell recruitment and increased fluid leakage into the airways. Notably, Adora2b-deficient mice failed to induce Tregs after endotoxin-induced inflammation and instead had an enhanced recruitment of pro-inflammatory effector T cells. In total, these data indicate that the Adora2b adenosine receptor serves a potent anti-inflammatory role, functioning at least in part through the enhancement of Tregs, to limit inflammation