Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development

Maternal Genome-Wide DNA Methylation Patterns and Congenital Heart Defects

The majority of congenital heart defects (CHDs) are thought to result from the interaction between multiple genetic, epigenetic, environmental, and lifestyle factors. Epigenetic mechanisms are attractive targets in the study of complex diseases because they may be altered by environmental factors and dietary interventions. We conducted a population based, case-control study of genome-wide maternal DNA methylation to determine if alterations in gene-specific methylation were associated with CHDs. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed maternal gene-specific methylation in over 27,000 CpG sites from DNA isolated from peripheral blood lymphocytes. Our study sample included 180 mothers with non-syndromic CHD-affected pregnancies (cases) and 187 mothers with unaffected pregnancies (controls). Using a multi-factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites, although no CpG site reached the most stringent level of genome-wide statistical significance. The majority of differentially methylated CpG sites were hypermethylated in cases and located within CpG islands. Gene Set Enrichment Analysis (GSEA) revealed that the genes of interest were enriched in multiple biological processes involved in fetal development. Associations with canonical pathways previously shown to be involved in fetal organogenesis were also observed. We present preliminary evidence that alterations in maternal DNA methylation may be associated with CHDs. Our results suggest that further studies involving maternal epigenetic patterns and CHDs are warranted. Multiple candidate processes and pathways for future study have been identified

Latest advances and future perspectives in Armillaria

The basidiomycete genus Armillaria s.l. (Armillaria s.s. and Desarmillaria) has a worldwide distribution and plays a central role in the dynamics of numerous woody ecosystems, including natural forests, tree plantations for timber production, orchards, vineyards and gardens. Early studies have shown that all Armillaria species are capable of degrading dead woody substrates, causing white rot. Moreover, most species exhibit a parasitic ability, and can be considered as facultative necrotrophs. Although over the years extensive research has been conducted on the phylogeny, biology and ecology of different Armillaria species, numerous theoretical and applied questions remain open. Recently published studies have provided new perspectives, the most significant of which we present in this review. First, new investigations have highlighted the importance of a multilocus approach for depicting the phylogeny of the genus Armillaria. Second, the importance of clonality and sexuality for the different species is now better described, enabling a more accurate prediction of population dynamics in various environments. Third, genome sequencing has provided new insights into genome evolution and the genetic basis of pathogenicity and wood degradation ability. Fourth, several new studies have pointed out the possible influence of climate change on Armillaria distribution, biology and ecology, raising questions regarding the future evolution of Armillaria species and their effect on ecosystems. In this review, we also give a state-of-the-art overview of the control possibilities of parasitic Armillaria species. Finally, we outline some still open questions in Armillaria research, the investigation of which will strongly benefit from recent methodological advances