- Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival
Natural killer (NK) cells eradicate virus-infected and transformed cells. Viant and colleagues describe the hierarchy of survival proteins and their apoptotic partners that govern NK cell survival. These data will inform approaches to harness NK cell activities in immunotherapies.
- Pharmacologic inhibition of Hsp90 to prevent GLT-1 degradation as an effective therapy for epilepsy
Sha et al. report that Hsp90β, which is up-regulated in astrocytes of human epileptogenic tissue, interacts with GLT-1 and recruits it to 20S proteasome for degradation. The Hsp90 inhibitor 17AAG exhibits beneficial effects in a model of temporal lobe epilepsy.
- Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity
Chen et al. dissect SAP-dependent and SAP-independent SLAM family signaling in the regulation of NKT cell development and follicular T helper cell differentiation using a novel mouse model lacking all seven SLAM family receptors.
- Peptidylarginine deiminase 4 promotes 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 controls ATG16L1 degradation to prevent ER stress during inflammation
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.
- The epidermal polarity protein Par3 is a non–cell autonomous suppressor of malignant melanoma
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.
- The EGR2 targets LAG-3 and 4-1BB describe and regulate dysfunctional antigen-specific CD8+ T cells in the tumor microenvironment
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.