Immuno Cover Image Design
Article: https://doi.org/10.3390/immuno4010004
Cover Story: Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by a vicious cycle of chronic inflammation and tissue destruction that stems from disruption of the skin microbiome and abnormal activation of both the innate and adaptive immune systems. A hallmark of HS pathophysiology is dysregulation of both the innate and adaptive immune systems. The role of immune system dysregulation in HS development has motivated researchers to explore the utility of biological immunomodulators. In this literature review, we provided an update on the efficacy and clinical usage of targeted biologics in HS treatment, including the use of anti-tumor necrosis factor-a, interleukin-17, interleukin-23, interleukin-1, C-X-C chemokine receptor 1/2, and Janus kinase inhibitors, among others.
Cell Host & Microbe Cover Image Design
Article: https://doi.org/10.1016/j.chom.2019.11.012
On the cover: Bacterial effectors manipulate host physiology through diverse mechanisms. In this issue, Gibbs et al. (129–139) and Panagi et al. (41–53) demonstrate that the secreted Salmonella SarA/SteE effector serves as a gp130 mimic, fooling the host into activating the transcription factor STAT3 to alter gene expression. To manipulate STAT3 activation, SarA/SteE alters the substrate specificity of GSK-3 kinase from serine/threonine to tyrosine residues. This mechanism reprograms host innate immune signaling by promoting M2 activation, which Pham et al. (54–67) demonstrates is required to overcome TNF-mediated suppression of Salmonella niche development in granulomas in vivo.
Cancer Cell
Cover Image Design
Article: https://doi.org/10.1016/j.ccell.2019.09.005
H3K27M mutations resulting in epigenetic dysfunction are frequently observed in diffuse intrinsic pontine glioma (DIPGs), an incurable pediatric cancer. We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. Mechanistically, Corin increases H3K27me3 levels suppressed by H3K27M histones, and simultaneously increases HDAC-targeted H3K27ac and LSD1-targeted H3K4me1 at differentiation-associated genes. Corin treatment induces cell death, cell-cycle arrest, and a cellular differentiation phenotype and drives transcriptional changes correlating with increased survival time in DIPG patients. These data suggest a strategy for treating DIPG by simultaneously inhibiting LSD1 and HDACs.