Issues

The editors at JEM share their views on gender bias in scientific publishing and their efforts to ensure that JEM remains a bias-free environment for all authors, reviewers, and editors.

Akiko Iwasaki: Women in STEM

Academic Editors at JEM share their experiences of being women in STEM and suggest future directions to support the career of female scientists.

Andrea D. Branch discusses the challenges of eliminating the burden of disease caused by HCV infection, despite the availability of curative antiviral treatments.

Toxoplasma gondii ROP16 is a virulence factor that modulates immune reposes acting in cis and in trans.

ncRNA-encoded polypeptide plays a big role in triple-negative breast cancer.

IL-34 is an alternative ligand for the colony stimulating factor-1 receptor. Here, the authors summarize recent advances of IL-34 in macrophage development and function and its role in health and disease.

IL-17A is a rational therapeutic target in RA; however, clinical trials have shown relatively modest success. This review explores possible reasons for the limited clinical efficacy of IL-17A blockade in RA, guided by recent insights in IL-17 biology.

IL-22 is a pleiotropic cytokine that acts in the regulation of host defense, barrier function, and metabolism. This review is focused on its physiological role in mucosal tissues in health and disease.

TGF-β is a central mediator in the fibrotic response. This review discusses the role of TGF-β in tissue fibrosis, highlighting the mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.

We characterized monocyte/macrophage populations from infants to older adults and lineage traced these cells using sex-mismatched lung transplant recipients. Classical monocytes peak in adulthood and decline in older adults. Importantly, our data show that after transplant, donor human airway macrophages (AMs) are readily replaced by recipient-derived monocytes.

Chen et al. identify patients with homozygous essential loss-of-function variants in human IL6ST that result in a complete loss of signaling of the whole family of GP130-dependent cytokines. This study identifies GP130 deficiency as the cause of an extended Stüve-Wiedemann syndrome.

Intestinal IgA is a key player in host-commensal symbiosis. Sterlin et al. report that human IgAs are microbiota cross-reactive at the clonal level. IgA1 and IgA2 mostly converge toward common gut microbiota targets but possess distinct carbohydrate repertoires.

An unexpected BDCA-2⁺CD123⁺CD1a⁺ DC subset comprises a major DC population in acute human sterile skin inflammation. scRNA-seq shows these to be activated DCs able to express markers normally associated with plasmacytoid DCs, prompting a re-evaluation of previous studies.

Ghaedi et al. identify IL-18R⁺IL-33R⁻ ILC progenitors, which differentiate into multiple ILC lineages, in the lung of neonatal and adult RORα lineage tracer mice. ILC2s in neonatal mouse lungs are divided into distinct cytokine and amphiregulin-producing effector ILC2s.

This work demonstrates a novel strategy that enables the identification of HCMV-derived T cell epitopes by mass spectrometry. It provides a panel of novel T cell epitopes and presents evidence for their involvement in physiologic immune control of HCMV infections.

The ability of T. gondii to promote a STAT3- and STAT6-dependent M2 phenotype in macrophages by injecting the virulence factor ROP16 in cis and trans subsequently limits the magnitude of the parasite-specific T cell response.

Microbiota-derived acetate coordinates innate immune responses during intestinal Clostridium difficile infection through its cognate receptor FFAR2. Acetate accelerates early neutrophil recruitment and increases ILC3 expression of the IL-1 receptor, boosting ILC3 production of IL-22 in response to neutrophil-derived IL-1β.

Huerga Encabo et al. show that NFAT5, previously characterized as a pro-inflammatory transcription factor, limits the IFN-I response to control antiviral defenses and preserve HSC quiescence. NFAT5 represses IFN-I and ISG expression through an evolutionarily conserved DNA element that prevents IRF3 recruitment to the IFNB1 enhanceosome.

In this issue, Malireddi et al. use a model of pathogen-induced priming and inhibition of TAK1 to demonstrate RIPK1 kinase activity–independent inflammasome activation and pyroptosis, apoptosis, and necroptosis that drive myeloid proliferation and sepsis in TAK1-deficient animals.

In this study, Wang et al. demonstrate that lncRNA-encoded polypeptide ASRPS is down-regulated in TNBC. ASRPS regulates angiogenesis and may serve as a novel prognostic marker and therapeutic target for TNBC.

Liu et al. build up an electron balance model for central carbon metabolism in cancer cells and reveal that simultaneous inhibitions of proline biosynthesis and lipogenesis can block cancer cell growth under hypoxia and in vivo tumor progress.

Kang et al. show that the hijacking of normally transiently induced pathways of myeloid regeneration by low Notch and high Wnt activity in hematopoietic stem cells is a common feature shared by myeloid leukemia that could be therapeutically targeted to control aberrant myeloid cell production.

Tieppo et al. show that the human fetal thymus generates invariant γδ T cells with programmed effector functions. This is due to an intrinsic property of fetal HSPCs caused by high expression of the RNA-binding protein Lin28b.

In germinal centers, B cells interact with antigen in the light zone and clonally expand in the dark zone. Davidzohn et al. show that BCR-induced Syk degradation in the light zone attenuates signal transduction, impedes plasma cell formation, and promotes B cell transition to the dark zone.

In basal keratinocytes, the nucleosome remodeler Mi-2β restricts access to gene regulatory elements associated with response to stress. Selective removal of Mi-2β causes rapid induction of AP1-regulated genes to restore barrier integrity. Reinstating Mi-2β at stress-response loci restores skin homesostasis.