Deadenylate or activate?: When cells are quiescent, they undergo reversible cell cycle arrest and evince low basal metabolism. Naïve T cells are normally quiescent until they recognize cognate antigens through T cell receptor–costimulatory molecule signaling. T cell quiescence appears to be an active process, but the mechanistic details are poorly understood. Hwang et al. report that the transcription factors BTG1 and BTG2 are selectively expressed in quiescent T cells. In mice, T cells conditionally knocked out for both factors showed enhanced proliferation and a lowered threshold of activation both in vitro and in response to Listeria monocytogenes infection. Deficiency of BTG1 and BTG2 resulted in increases in global messenger RNA half-life, suggesting that messenger RNA deadenylation and degradation are important processes for maintaining T cell quiescence. Science , this issue p. 1255

Caspases are crucial regulators of programmed cell death, mediating pathways such as apoptosis, pyroptosis, necroptosis and ferroptosis. Their activity is intricately controlled by epigenetic modifications, molecular interactions and post-translational changes, reflecting their central role in cellular homeostasis and disease mechanisms. Dysregulated caspase functions are linked to a wide array of conditions, including cancer, neurodegenerative disorders and inflammatory diseases, establishing their importance as potential therapeutic targets. The roles and regulation of caspases across subcellular compartments and their molecular interactions provide critical insights into the complexity of programmed cell death. Here, this review synthesizes current knowledge on the diverse functions of caspases, offering a comprehensive foundation for exploring innovative therapeutic strategies.

Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood–brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.

Dho SH, et al. Immune Netw. 2018 Jan;18:e11. https://doi.org/10.4110/in.2018.18.e11