- PAD4 regulates age-related organ fibrosis
Peptidylarginine deiminase 4 (PAD4) citrullinates proteins. In neutrophils, it causes chromatin decondensation and release of NETs, which are injurious. Martinod et al. show in this study that NETs promote fibrosis in a cardiac model and that PAD4-deficient mice have reduced age-related organ fibrosis.
- IKKα stabilizes ATG16L1
Decreased ATG16L1 stabilization is associated with increased susceptibility to develop inflammatory bowel diseases. Diamanti et al. identify IKKα as a central upstream kinase of ATG16L1, providing evidence that ATG16L1 stabilization is controlled by phosphorylation downstream of TNF and NOD activation.
- Epidermal Par3 controls melanoma via P-cadherin
Mescher et al. uncover a novel tissue-borne tumor suppression mechanism, engaging polarity proteins in the epithelial microenvironment that prevent malignant outgrowth of neighboring cell types through control of heterologous cell–cell contacts. Moreover, their data support an emerging role of P-cadherin, which is frequently amplified in human carcinoma, as a protumorigenic and proinvasive adhesion molecule, thus placing it as a promising druggable target to disrupt tumor–microenvironment interactions for anticancer therapy.
- LAG-3 and 4-1BB describe dysfunctional TIL
Williams et al. show that 4-BB and LAG-3, previously identified as EGR2 targets from in vitro T cell anergy studies, are sufficient to identify dysfunctional tumor antigen–specific CD8+ T cells in the tumor microenvironment. These markers facilitated detailed transcriptional and phenotypic characterization and provided therapeutic targets for tumor control.
- CD70/CD27 signaling promotes blast stemness in AML
Riether et al. show that CD70/CD27 signaling activates stem cell gene expression programs in acute myeloid leukemia (AML). Blocking the CD70/CD27 interaction inhibits self-renewal and induces differentiation of AML blasts and stem/progenitor cells.
- WNT-5A impairs alveolar epithelial cell repair
Baarsma et al. report increased expression and posttranslational modification of the noncanonical ligand WNT-5A in COPD. Fibroblast-derived WNT-5A inhibits canonical WNT–β-catenin–driven alveolar epithelial cell–mediated wound healing and transdifferentiation, and thus contributes to impaired lung regeneration and COPD pathogenesis.
- ILC2 activation by leukotrienes
von Moltke et al. demonstrate that optimal cytokine induction in group 2 innate lymphocytes results from synergy between NFAT-dependent leukotriene signaling and IL-33 signaling. This integration of signaling pathways may represent an innate substitute for the T cell receptor.
- PFIT caused by mutation in 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.