Highlight of 2023: Virtues and vices of CD4 CAR T cells.

This article for the Highlights of 2023 Series explores recent work that suggests that targeting CD4 CAR T cells may be critical for both of these challenges.

Skeletal muscle ageing: lessons from teleosts.

Ageing is the greatest risk factor for a multitude of age-related diseases including sarcopenia -the loss of skeletal muscle mass and strength - which occurs at remarkable rates each year. There is an unmet need not only to understand the mechanisms that drive sarcopenia, but also to identify novel therapeutic strategies. Given the ease and affordability of husbandry, along with advances in genomics, genome editing technologies and imaging capabilities, teleost models are increasingly used for ageing and sarcopenia research. Here, we explain how teleost species such as zebrafish, African turquoise killifish and medaka recapitulate many of the classical hallmarks of sarcopenia, and discuss the various dietary, pharmacological and genetic approaches that have been used in teleosts to understand the mechanistic basis of sarcopenia.

Insights into H2O2-induced signaling in Jurkat cells from analysis of gene expression.

Hydrogen peroxide (H2O2) is a ubiquitous oxidant produced in a regulated manner by various enzymes in mammalian cells. H2O2 reversibly oxidizes thiol groups of cysteine residues to mediate intracellular signaling. While examples of H2O2-dependent signaling have been reported, the exact molecular mechanism(s) of signaling and the pathways affected are not well understood. Here, the transcriptomic response of Jurkat T cells to H2O2 was investigated to determine global effects on gene expression. With a low H2O2 concentration (10 µM) that did not induce an oxidative stress response or cell death, extensive changes in gene expression occurred after 4 h (6803 differentially expressed genes). Of the genes with a greater then 2-fold change in expression, 85% were upregulated suggesting that in a physiological setting H2O2 predominantly activates gene expression. Pathway analysis identified gene expression signatures associated with FOXO and NTRK signaling. These signatures were associated with an overlapping set of transcriptional regulators. Overall, our results provide a snapshot of gene expression changes in response to H2O2, which, along with further studies, will lead to new insights into the specific pathways that are activated in response to endogenous production of H2O2, and the molecular mechanisms of H2O2 signaling.