- Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1
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.
- Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE
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.
- Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like receptor–mediated inflammatory responses
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.
- Niche WNT5A regulates the actin cytoskeleton during regeneration of hematopoietic stem cells
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.
- Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles
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.
- Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency–induced autoimmunity via adenosine A2A receptors
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 A2A receptor. This finding establishes a link between the gut microbiota, A2A receptors, and autoimmunity induced by T reg cell deficiency.
- Estrogen activation of microglia underlies the sexually dimorphic differences in Nf1 optic glioma–induced retinal pathology
Toonen et al. show that estrogen increases microglia-mediated retinal damage in neurofibromatosis-1 (Nf1) optic glioma.
- Combined immunodeficiency and Epstein-Barr virus–induced B cell malignancy in humans with inherited CD70 deficiency
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.