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Clonal hematopoiesis of indeterminate potential (CHIP) promotes osteoporosis via bone-resorbing osteoclasts.

Viewpoint

Laura Kirkman and Roland Cooper discuss how repurposing drugs can play a role in controlling malaria.

Here, Katrin Mayer-Barber and Clifton Barry III discuss patterns and pathways associated with individuals infected with Mycobacterium tuberculosis who develop clinical symptoms.

Brief Definitive Reports

Somatic mutations such as in DNMT3A accumulate in hematopoietic stem cells in CHIP. Kim et al. show that CHIP promotes osteoporosis via bone-resorbing osteoclasts. Mutant macrophages with altered methylation and inflammatory signaling secrete cytokines such as IL-20.

Tristetraprolin (TTP) negatively regulates constitutive IL-5 and IL-13 production in group 2 innate lymphoid cells (ILC2s) through mRNA degradation. In Zfp36−/− mice, eosinophilopoiesis was dysregulated by IL-5 overproduction in ILC2s, suggesting that TTP is crucial in regulating ILC2 homeostatic function.

Articles

The authors report inborn error of TLR3 or MDA5 in two unrelated children with enterovirus rhombencephalitis. TLR3 and MDA5 may control anti-enterovirus immunity in central nervous system cells via the maintenance of basal or virus-induced type I IFN production, respectively.

Activation of PI3Kδ signaling in B cells impairs autophagy, leading to increased ER stress and plasma cell death in an mTORC1-dependent mechanism.

We report four patients in a multigenerational family carrying a novel heterozygous variant in AIOLOS/IKZF3 associated with T and B cell developmental and functional defects, CID, PJP, and CLL. Identification of germline IKZF3 mutations introduces us to hereditary AIOLOS-associated diseases in humans.

Shinnakasu et al. show that the glycan engineering immunogens of SARS-CoV-2 spike receptor-binding domain (RBD) elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibodies, thereby manifesting significant neutralizing activity not only for SARS-CoV-2 but also for more broad SARS-related viruses.

Through single-cell TCR and RNA sequencing, the authors identified public cTfh clonotypes expanded in recovered COVID-19 patients and determined their epitopes in the specific regions of spike protein conserved among emerging SARS-CoV-2 variants, which are candidates for booster antigens.

Antibodies are central to long-term protection after infection or vaccination but often compromised in infancy. This study identifies a mechanism by which this compromise occurs and shows how it can be targeted to boost antibodies in early life and provide protection from reinfection.

This study combines HIV-1 sequence analysis and integration site discovery to show a preponderance of integrations into ZNF genes in expanded latent clones. ZNF genes, unlike other integration targets, are downregulated upon T cell activation, which may facilitate latency maintenance.

Isringhausen et al. demonstrate that chronic viral infection causes durable destruction of BM mesenchymal stromal networks and leads to long-lasting impairment of the competitive fitness of HSCs. In vivo blockage of IFN pathways protects BM and HSC function from viral-induced damage.

The histone demethylase Lsd1 is required for down-regulation of stem cell and early progenitor genes and for the activity of several repressive transcription factors, including Bcl11b, Gfi1, and Bcl6, during T cell development.

The authors find that lung and skin pathogenic CD4+ T cells express high levels of ACC1. ACC1 controls the inflammatory function of the pathogenic CD4+ T cell population to promote type 2 inflammation in the lung and skin.

In Special Collection:
JEM Cancer Immunotherapy 2021

Zhang, Kim, and colleagues reveal two macrophage subpopulations lining peritoneal surfaces that are distinct from peritoneal fluid macrophages. One population expresses LYVE1, resembles omental macrophages, and promotes expansion of ovarian cancer within the cavity in the absence of the omentum.

HVEM is a TNF family receptor that binds a TNF protein and Ig family proteins. Using structural biology and mutagenesis, we identified HVEM muteins with selective ligand binding. We verified their function in vivo in models of inflammation and infection.

Asialo-biantennary N-glycan is identified as a ligand for the inhibitory C-type lectin receptor DCIR, which is important for the homeostasis of the immune and bone system. The interaction between DCIR and asialo-biantennary N-glycans negatively regulates antigen presentation by DCs and osteoclastogenesis.

This study demonstrates that peripheral nerve injury–induced downregulation of ZNF382 in DRG contributes to neuropathic pain likely through silencer-based epigenetic disinhibition of CXCL13, a key neuropathic pain player, in DRG neurons.

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