ON THE COVER
Stockenhuber et al. demonstrate that Foxp3+ regulatory T cells control psoriasiform skin inflammation by restraining a type 1 interferon–driven CD8+ T cell response. The cover is representative H&E staining of ear tissue cross sections. The image was taken from the original manuscript and modified by the JEM editorial office. See page 1987.
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In this issue of JEM, Nakajima et al. demonstrate that glycan-dependent, epitope-independent IgA coating of intestinal bacteria alters bacterial gene expression and metabolism. This conferred coated bacteria with fitness within the mucus niche and contributed to intestinal homeostasis through cross-phylum interactions.
In this issue of JEM, Arnold et al. demonstrate that eosinophils suppress mucosal inflammation by directly interacting with pro-inflammatory Th1 cells. This emphasizes the dual role of eosinophils, which can act both as effector cells that control an infection and as immunomodulatory cells that promote immune homeostasis.
In this issue of JEM, Umemoto et al. demonstrate that calcium influx stimulates mitochondrial metabolism and initiates proliferation in hematopoietic stem cells (HSCs). Extracellular adenosine, sourced from surrounding hematopoietic progenitors, inhibits this calcium influx, thereby suppressing mitochondrial metabolism and promoting HSC quiescence. This is the first demonstration that a calcium–mitochondria pathway regulates HSC division.
Brief Definitive Report
This study presents a comprehensive lesion-centric analysis of disease progression in the rabbit model of tuberculosis, showing immunopathology and lesion heterogeneity similar to human and nonhuman primates. In this model, pyrazinamide sterilizes necrotic lesions, where persistent bacterial populations reside.
Foxp3+ T reg cells control psoriasiform inflammation by restraining an IFN-I–driven CD8+ T cell response
Stockenhuber et al. demonstrate that Foxp3+ regulatory T cells control psoriasiform skin inflammation by restraining a type I interferon (IFN-I)–driven CD8+ T cell response. The absence of T reg cells led to exacerbated inflammation, infiltration of CD8+ T cells to the epidermis, and an IFN-I gene signature in the tissue.
CRL4DCAF2 negatively regulates IL-23 production in dendritic cells and limits the development of psoriasis
Deregulated NF-κB activation is linked to immunological disorders. Huang et al. revealed CRL4DCAF2 as a negative regulator in controlling NIK stability in DCs. Lower level of DCAF2 is associated with noncanonical NF-κB activation and hyperproduction of IL-23 in psoriasis patients.
IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria
IgA regulates the composition and function of gut microbiota. Nakajima et al. show that a heavily glycosylated monoclonal IgA coats B. theta and induces Mucus-Associated Functional Factor in vivo to enhance symbiotic interactions with commensal bacteria to maintain gut homeostasis.
A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses
Le Gallou et al. use an AID fate-mapping model to identify an IgM memory population in the spleen of unimmunized mice, originating from persistent gut immune responses and endowed with cross-reactivity against bacteria.
Arnold et al. report that eosinophils in the gastrointestinal tract are conditioned by IFN-γ to restrict Th1 responses and promote tissue homeostasis. Eosinophils control Th1 cells in acute and chronic infection and in the steady state and possess bactericidal properties.
PIK3CD mutations cause immune dysregulation. By studying humans and a novel mouse model, we show these mutations intrinsically impair B-cell development and function. These findings reveal mechanisms of compromised humoral immunity due to PIK3CD mutations, and opportunities to pharmacologically restore these defects.
The activation of Ca2+–mitochondria pathway drives cell division in hematopoietic stem cells, and the level of its activity is critical to determine cell fate after HSC division. Extracellular adenosine contributes to the regulation of Ca2+–mitochondria pathway in HSCs in vivo.
Through functional screening of a miR-196b target network in the poor prognosis subgroup of MLL-rearranged AML, Meyer et al. reveal a therapeutically targetable Skp2/p27Kip1 regulatory axis that modulates leukemic stemness, differentiation, and survival.
Stolte et al. use genome-scale CRISPR-Cas9 screening technology to identify druggable targets for TP53 wild-type Ewing sarcoma and discover reactivation of p53 through inhibition of MDM2, MDM4, Wip1, or USP7 as therapeutic strategies for the disease.
ILC2s are key players in allergic airway inflammation. Lei et al. show that ICAM-1 controls ILC2 development and function through regulating ERK signaling pathway, suggesting targeting ICAM-1 as a potential strategy for ILC2-induced asthma.
Th2 response is implicated in the pathogenesis of PAH. Chen et al. demonstrate that CRTH2-mediated Th2 activation is exaggerated in patients with PAH and mouse PAH models, and pharmacological inhibition of CRTH2 attenuates experimental PAH by suppression of IL-4 and IL-13.
Kimura et al. demonstrate that NQO1 plays a crucial role in degrading IκB-ζ protein through forming the complex together with PDLIM2 and selectively suppresses IL-6 and IL-12 production induced by TLR ligands.
Xing et al demonstrate the requirements for Tle transcriptional corepressors in CD8+ T cell development. Tle proteins are differentially partitioned to the Runx and Tcf/Lef complexes to promote CD8+ lineage choice and establish CD8+ T cell identity, respectively.