Plant NLR-type receptors serve as sensitive triggers of host immunity. Their expression has to be well-balanced, due to their interference with various cellular processes and dose-dependency of their defense-inducing activity. A genetic “arms race” with fast-evolving pathogenic microbes requires plants to constantly innovate their NLR repertoires. We previously showed that insertion of the COPIA-R7 retrotransposon into RPP7 co-opted the epigenetic transposon silencing signal H3K9me2 to a new function promoting expression of this Arabidopsis thaliana NLR gene. Recruitment of the histone binding protein EDM2 to COPIA-R7-associated H3K9me2 is required for optimal expression of RPP7. By profiling of genome-wide effects of EDM2, we now uncovered additional examples illustrating effects of transposons on NLR gene expression, strongly suggesting that these mobile elements can play critical roles in the rapid evolution of plant NLR genes by providing the “raw material” for gene expression mechanisms. We further found EDM2 to have a global role in NLR expression control. Besides serving as a positive regulator of RPP7 and a small number of other NLR genes, EDM2 acts as a suppressor of a multitude of additional NLR genes. We speculate that the dual functionality of EDM2 in NLR expression control arose from the need to compensate for fitness penalties caused by high expression of some NLR genes by suppression of others. Moreover, we are providing new insights into functional relationships of EDM2 with its interaction partner, the RNA binding protein EDM3/AIPP1, and its target gene IBM1, encoding an H3K9-demethylase. We previously found the Arabidopsis thaliana PHD-finger protein EDM2 to serve as a chromatin-associated factor controlling expression of the NLR-type immune receptor gene RPP7. EDM2 binds to the transposon-silencing signal H3K9me2 and affects levels of this epigenetic mark at various loci. By genome-wide profiling of transcript- and H3K9me2-levels we now found EDM2 to have a broader role in controlling NLR gene expression. In order to mitigate fitness costs caused by its promoting effects on RPP7 expression and that of several other NLR genes, EDM2 seems to suppress expression of many additional members of this gene family. This observation is in line with multiple reports demonstrating the need for balanced expression of NLRs, which can substantially reduce overall plant fitness, but need to be present at certain minimal levels to confer sufficient immune protection. Our previous results demonstrated that the influence of EDM2 on RPP7 expression was co-opted to this immune receptor gene by the insertion of an EDM2-controlled transposon. Here, we are providing additional examples for transposon-associated effects on NLR gene expression, suggesting that these mobile elements play an important role for NLR genes by equipping members of this rapidly evolving gene family with regulatory mechanisms needed for balanced expression.

Sepsis remains a common cause of death in intensive care units, accounting for approximately 20% of total deaths worldwide. Its pathogenesis is partly attributable to dysregulated inflammatory responses to bacterial endotoxins (such as lipopolysaccharide, LPS), which stimulate innate immune cells to sequentially release early cytokines (such as tumor necrosis factor (TNF) and interferons (IFNs)) and late mediators (such as high-mobility group box 1, HMGB1). Despite difficulties in translating mechanistic insights into effective therapies, an improved understanding of the complex mechanisms underlying the pathogenesis of sepsis is still urgently needed. Here, we review recent progress in elucidating the intricate mechanisms underlying the regulation of HMGB1 release and action, and propose a few potential therapeutic candidates for future clinical investigations.