- 17AAG prevents GLT-1 degradation in 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.
- NKT and TFH cells in SFR-deficient mice
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.
- DC lethargy under T reg cell binding
Chen et al. show that regulatory T cells adhere to dendritic cells (DCs) with high binding forces. This strong binding causes cytoskeletal polarization in the latter, which limits DCs’s ability to form productive engagement with other antigen-specific T cells.
- MHC-independent T reg cell suppression of DCs in vivo
Yan et al. demonstrate that in vivo T reg cells can form prolonged contacts with dendritic cells (DCs) in an MHC-independent manner and suppress the ability of the same DCs to contemporaneously engage in stable interactions with and activate conventional T cells.
- 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.