Issues

Kate Schroder is a professor and director of the Centre for Inflammation and Disease Research at the Institute for Molecular Bioscience (IMB), University of Queensland, Australia. Her lab, the IMB Inflammasome Laboratory, is interested in the mechanisms that underlie inflammasome activity and inhibition, regulators of inflammasome-dependent inflammation, and caspase activation.

Defective microglial responses underlie many neurological disorders. Recent efforts to swap out dysfunctional microglia with optimized replacements have been derailed by safety issues and transplantation inefficiencies. In this issue, Chadarevian et al. designed a novel strategy that enables improved engraftment of human microglia.

Oral wounds heal exceptionally fast with minimal scarring, but the mechanism is unclear. Ko and colleagues show that distinct oral fibroblast progenitors differentiate into highly chemotactic fibroblasts, which promote transient macrophage response and resolution of inflammation to expedite the healing process.

In this issue of JEM, Chu and An et al. describe the role of the tricyclic antidepressant nortriptyline in inhibition of fatty acid uptake. Nortriptyline promotes cell acidification and suppresses macropinocytosis, providing a link between fatty acid uptake and tumor progression.

Andre Buret and Thibault Allain discuss the mechanisms that regulate gut microbiota biofilms integrity and highlight the importance of studying phenotypic biofilm damage, beyond the characterization of relative bacterial abundance.

The microbiome influences response to immunotherapy, including immune-related adverse events (irAEs) with checkpoint inhibitors. Wang, Jenq, et al. discuss microbiome contributions to irAEs by focusing on major bacterial taxa, potential immune mechanisms, and clinical opportunities for microbiome modulation to treat irAEs.

STING signaling is at the center of multiple autoinflammatory and neurodegenerative diseases. The authors review how STING trafficking influences signaling, propose a model of tonic STING signaling, and discuss an emerging link between dysregulated STING trafficking and neurodegenerative disease.

A G795A substitution in human colony stimulating factor 1 receptor (CSF1R) confers resistance to pharmacological inhibitors, enabling widespread engraftment of human microglia and murine macrophages within the brain, and providing a highly efficient strategy to replace microglia in a nontoxic, cell type, and tissue-specific manner.

The underlying mechanisms that drive Th1 responses in the intestine remain unclear. Here, Ahmadi and coworkers show that the microbiota-dependent post-weaning accumulation of Th1 cells in the intestine is dependent on cDC1 expression of MHC-II and IL-27.

Oral wounds heal exceptionally fast with minimal scarring, but the mechanism is unclear. Ko and colleagues show that distinct oral fibroblasts differentiate into highly chemotactic fibroblasts, which promote transient macrophage response and resolution of inflammation to expedite the healing process.

Chu et al. identify a clinical drug, nortriptyline that can potently inhibit macropinocytosis-mediated fatty acid uptake, and further find that nortriptyline effectively suppresses tumor growth, lipogenesis, and hepatic steatosis in combination with ND-646, a selective ACC1/2 inhibitor.

Inhibition of CDK4/6 and lysosome function overcomes c-MYC–mediated cell cycle entry in the face of trametinib and chloroquine co-treatment in pancreatic cancer.

This study unveils that OBP2A from PCa in remission during ADT enhances PCa growth and MDSCs infiltration through interaction with CXCL15/IL8, leading to CRPC emergence. Targeting OBP2A of tumor in remission would be effective therapeutic strategy for advanced PCa.

DNA-damaging cancer therapies induce delayed activation of cGAS–STING-dependent type I interferon signaling in the heart. DNA damage–induced cGAS–STING signaling drives cardiac inflammation and late pathologic remodeling of the heart, progressive cardiac functional impairment, and late lethal cardiac toxicity.

Here, Hodge et al. demonstrate large neutral amino acid transporters regulate the magnitude of ILC2 responses. Amino acid uptake controls ILC2 expansion in part via mTOR. These findings expand understanding of nutrient regulation of innate immunity at mucosal barrier sites.

During influenza virus infection, Treg cell–derived amphiregulin is sensed by EGFR⁺Collagen-14⁺ lung mesenchymal cells, stimulating their activation and survival and supporting their role as signaling relay intermediates to promote effective alveolar regeneration.

We show suppression of CD4 effector T cell activation by Tregs is enforced through active mRNA translational control of the protein synthesis machinery. We show proof-of-concept therapeutic targeting of protein synthesis that leads to the mitigation of inflammatory responses invoked by Treg loss of function.

The WNK1 kinase is essential in B cells for T-dependent antibody responses because it is activated by signaling from BCR, CXCR5, and CD40, and regulates B cell migration, adhesion, T-dependent activation, and differentiation into germinal center B cells and plasma cells.

Functional recovery after spinal cord injury is guided by the formation of new spinal detour circuits. The authors show that the formation of these circuits is enhanced by targeted chemogenetic stimulation of supraspinal and spinal neuron populations. Supraspinal and spinal coordinated stimulation potentiated behavioral recovery.