Issues

As Co-Chairs and Executive Editor of The Journal of Experimental Medicine, we write to share some changes that will help us provide JEM authors with the best service we can.

Toonen et al. show that estrogen increases microglia-mediated retinal damage in neurofibromatosis-1 (Nf1) optic glioma.

von Moltke et al. demonstrate that optimal cytokine induction in group 2 innate lymphocytes results from synergy between NFAT-dependent leukotriene signaling and IL-33 signaling. This integration of signaling pathways may represent an innate substitute for the T cell receptor.

Nish et al. report that production of a fully committed Th1 effector cell occurs during an asymmetric cell division wherein the other daughter cell remains memory cell–like. Unequal transmission of metabolic signaling may be the driver of this regenerative behavior.

Wang et al. show that antibody gene deamination by activation-induced cytidine deaminase (AID) is restricted to a short time window in early G1 as a result of AID’s transient nuclear localization and accessibility of the target sites.

Standing et al. report a novel autoinflammatory disease caused by a homozygous missense mutation in the actin-regulating protein WDR1. The disease is characterized by periodic fevers, immunodeficiency, and thrombocytopenia, with increased polymerized actin in immune cells and increased IL-18 secretion.

Izawa et al. identify the first patient with CD70 deficiency suffering from recurrent EBV-induced B cell proliferations including Hodgkin’s lymphoma. Expression of CD70 on B cells is necessary to induce proliferation of EBV-specific T cells.

Abolhassani et al. show that CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of CD27 deficiency. CD70–CD27 interactions play a nonredundant role regulating humoral- and cell-mediated immunity in humans, especially for control of EBV.

He et al. show that T reg deficiency markedly induces autoimmunity and shifts gut microbiota. Remodeling microbiota by Lactobacillus reuteri was found to inhibit autoimmunity via the metabolite inosine, which interacts with the adenosine A_2A receptor. This finding establishes a link between the gut microbiota, A_2A receptors, and autoimmunity induced by T reg cell deficiency.

Connor et al. show that transcriptomic profiling of DCs exposed to two different Th2 stimuli in vivo reveals large numbers of differentially expressed genes but few similarities between conditions.

Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD. Fibroblast-derived WNT-5A inhibits canonical WNT–β-catenin–driven alveolar epithelial cell–mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.

Schreck et al. show that environmental Wnt5a regulates the transcriptome of HSCs during regeneration, particularly the expression of actin-regulatory mediators. In this manner, the niche affects engraftment through regulation of adhesion, migration, and homing of both normal and malignant cells.

Combining novel mouse reporters and single-cell transcriptomic analyses, Wu et al. uncover differential activation thresholds for the transcripts that direct antibody class switching to IgE versus IgG1 in response to IL-4 and explain how cell-intrinsic transcriptional heterogeneity governs CSR.

Vaidyanathan et al. report that the environmental sensor aryl hydrocarbon receptor is inducibly expressed in B cells downstream of BCR signaling and that it controls B cell fates by negatively modulating class switching and plasma cell differentiation via aicda and prdm1, respectively.

Xu et al. show that LRCH1 interferes with the GEF activity of DOCK8 to inhibit Cdc42 activation. Upon chemokine stimulation, DOCK8 is phosphorylated and released from LRCH1 to drive cell migration. LRCH1 overexpression reduces CD4⁺ T cell migration to the CNS and ameliorates experimental autoimmune encephalomyelitis.

Westphal et al. demonstrate a role of lysosomal trafficking regulator Lyst that couples the regulation of endolysosomal trafficking to inflammatory responses by the control of toll-like receptor–mediated endosomal TRIF signaling pathways.

Fang et al. show that the deubiquitinase USP13 stabilizes c-Myc in glioblastoma stem cells (GSCs) by counteracting FBXL14-mediated Myc ubiquitination. c-Myc stabilization maintains GSC self-renewal and tumorigenic potential.