Decreased Numbers of Blood Dendritic Cells and Defective Function of Regulatory T Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

BACKGROUND: Dendritic cells (DC) and regulatory cells (Treg) play pivotal roles in controlling both normal and autoimmune adaptive immune responses. DC are the main antigen-presenting cells to T cells, and they also control Treg functions. In this study, we examined the frequency and phenotype of DC subsets, and the frequency and function of Treg from patients with ANCA-associated vasculitis (AAV). METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from 19 untreated patients with AAV during flares and before any immunosuppressive treatment were analyzed, along with 15 AAV patients in remission and 18 age-matched healthy controls. DC and Treg numbers, and phenotypes were assessed by flow cytometry, and in vitro suppressive function of Treg was determined by co-culture assay. When compared to healthy volunteers, absolute numbers of conventional and plasmacytoid DC were decreased in AAV patients. During the acute phase this decrease was significantly more pronounced and was associated with an increased DC expression of CD62L. Absolute numbers of Treg (CD4(+)CD25(high)CD127(low/-) Tcells) were moderately decreased in patients. FOXP3 and CD39 were expressed at similar levels on Treg from patients as compared to controls. The suppressive function of Treg from AAV patients was dramatically decreased as compared to controls, and this defect was more pronounced during flares than remission. This Treg functional deficiency occurred in the absence of obvious Th17 deviation. CONCLUSION: In conclusion, these data show that AAV flares are associated with both a decrease number and altered phenotype of circulating DC and point to a role for Treg functional deficiency in the pathogenesis of AAV

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Identifying sequence features impacting recombination in wheat: lessons from chromosome 3B

ISBN: 978-3-900932-48-0Book of abstracts p.33Identifying sequence features impacting recombination in wheat: lessons from chromosome 3B. 13. Int. Wheat Genet. Sym

Genome sequence of fusarium graminearum strain MDC_Fg1, isolated from bread wheat grown in France

International audienceFusarium graminearum is a major fungal pathogen that induces Fusarium head blight (FHB), a devastating disease of small-grain cereals worldwide. This announcement provides the whole-genome sequence of a highly virulent and toxin-producing French isolate, MDC_Fg1

Structural variations of the hexaploid wheat chromosome 3B

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All families of transposable elements were active in the recent wheat genome evolution and polyploidy had no impact on their activity

International audienceBread wheat (Triticum aestivum L.) is a major crop and its genome is one of the largest ever assembled at reference-quality level. It is 15 Gb, hexaploid, with 85% of transposable elements (TEs). Wheat genetic diversity was mainly focused on genes and little is known about the extent of genomic variability affecting TEs, transposition rate, and the impact of polyploidy. Multiple chromosome-scale assemblies are now available for bread wheat and for its tetraploid and diploid wild relatives. In this study, we computed base pair-resolved, gene-anchored, whole genome alignments of A, B, and D lineages at different ploidy levels in order to estimate the variability that affects the TE space. We used assembled genomes of 13 T. aestivum cultivars (6x = AABBDD) and a single genome for Triticum durum (4x = AABB), Triticum dicoccoides (4x = AABB), Triticum urartu (2x = AA), and Aegilops tauschii (2x = DD). We show that 5%-34% of the TE fraction is variable, depending on the species divergence. Between 400 and 13,000 novel TE insertions per subgenome were detected. We found lineage-specific insertions for nearly all TE families in di-, tetra-, and hexaploids. No burst of transposition was observed and polyploidization did not trigger any boost of transposition. This study challenges the prevailing idea of wheat TE dynamics and is more in agreement with an equilibrium model of evolution

Location and Identification on Chromosome 3B of Bread Wheat of Genes Affecting Chiasma Number

International audienceUnderstanding meiotic crossover (CO) variation in crops like bread wheat (Triticum aestivum L.) is necessary as COs are essential to create new, original and powerful combinations of genes for traits of agronomical interest. We cytogenetically characterized a set of wheat aneuploid lines missing part or all of chromosome 3B to identify the most influential regions for chiasma formation located on this chromosome. We showed that deletion of the short arm did not change the total number of chiasmata genome-wide, whereas this latter was reduced by ~35% while deleting the long arm. Contrary to what was hypothesized in a previous study, deletion of the long arm does not disturb the initiation of the synaptonemal complex (SC) in early meiotic stages. However, progression of the SC is abnormal, and we never observed its completion when the long arm is deleted. By studying six different deletion lines (missing different parts of the long arm), we revealed that at least two genes located in both the proximal (C-3BL2-0.22) and distal (3BL7-0.63-1.00) deletion bins are involved in the control of chiasmata, each deletion reducing the number of chiasmata by ~15%. We combined sequence analyses of deletion bins with RNA-Seq data derived from meiotic tissues and identified a set of genes for which at least the homoeologous copy on chromosome 3B is expressed and which are involved in DNA processing. Among these genes, eight (CAP-E1/E2, DUO1, MLH1, MPK4, MUS81, RTEL1, SYN4, ZIP4) are known to be involved in the recombination pathway

Comparative genomics of two Fusarium graminearum strains of contrasting aggressiveness in bread wheat

By targeting host cellular processes, fungal effectors promote growth and spreading of pathogenic fungi in plant tissues. During the wheat/Fusarium graminearum (Fg) interaction causing the Fusarium head blight (FHB) disease, the nature and the function of these fungal molecular components which control plant susceptibility factors, remain largely unknown. Two Fg strains (Fg1 and Fu10008) contrasting for their aggressiveness in field trials were sequenced using Sequel technology. Fg1 and Fu10008 displayed 11,171 CDS (37,2Mb) and 10,629 CDS (36,1Mb), respectively. The comparative analysis of the predicted proteomes revealed 1,320 specific proteins in Fg1 and 693 in Fu10008, comprising 205 and 81 candidate putative effectors, respectively. A thorough pathotyping of the two Fg strains on three wheat genotypes of different susceptibility to FHB was assessed to test their mycotoxin production and their infection dynamics, including symptoms development and fungal biomass progress in point-inoculated spikelets (PI) and in the uninoculated peripheral ones (Up or Dn). Fg1 strain induced systematically the most severe symptoms in the PI, Up and Dn parts of each wheat genotypes. Whatever the infected genotype, Fg1 initiated symptom development 24 h earlier than Fu10008. Spreading of both strains in Up and Dn spikelets appeared preferentially towards the top of the spike as early as 5 days post-inoculation, displaying symptoms very close to those of the PI parts suggesting that they are related to fungal migration in healthy plant tissues. qRT-PCR and mycotoxin analyzes (DON and ZEA) of the different spike zones are currently performed to refine the early stages of the infection process of both strains. This will allow for connecting these Fg data to recent work investigating the wheat susceptibility factors (Chetouhi et al., 2016) and will contribute to shape an integrated picture of the molecular events piloting FHB

Deciphering strucutral variation in wheat genome using resequencing data

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