Schaefer, S. K. | Search bioRxiv

bioRxiv2021

STAT1 Gain-of-Function Variants Drive Altered T Cell Prevalence, Metabolism, and Heightened IL-6 Sensitivity

Patients with Signal Transducer and Activator of Transcription 1 (STAT1) gain-of-function (GOF) pathogenic variants exhibit susceptibility to infections, autoimmunity, and cancer due to enhanced or prolonged STAT1 phosphorylation following cytokine stimulation. While interferons (IFNs) are canonical STAT1 activators, other cytokines that may also contribute to pathology in STAT1 GOF patients have been less well defined. Here we analyzed the immune profiles and cytokine responses of two patients with heterozygous GOF mutations in the STAT1 coiled-coil domain. A systems immunology approach revealed major changes in the T cell compartment and minor changes in the B cells, NK cells, and myeloid cells. Both patients with STAT1 GOF differed from healthy individuals in the abundance and phenotype of effector memory, Th17, and Treg populations. STAT1 GOF T cells displayed a pattern of increased activation and had elevated markers of glycolysis and lipid oxidation. Hypersensitivity of T cells to IL-6 was observed with intense, sustained STAT1 phosphorylation in memory T cell populations that exceeded that induced by IFNs. Together, these results show a role for STAT1 in T cell metabolism and suggest that IL-6 may play a critical role to promote T cell memory formation and activation in patients with STAT1 GOF.

immunology↗

bioRxiv2019

Sleep’s impact on emotional memory: A meta-analysis of whole-night, nap, and REM sleep effects

Numerous studies have shown that sleep enhances the consolidation of episodic memory. However, it remains unclear whether this consolidation benefit is moderated by the emotional valence of the learned material. To clarify whether sleep selectively enhances the consolidation of emotional material, we conducted a meta-analysis including N = 1,059 observations. Overall, our results do not support this hypothesis. When only studies with a sleep-group wake-group comparison were included in the analysis (k = 22), the retention advantage for emotional over neutral material was not significantly different between sleep and wake groups. When studies initially lacking a wake-control group were included in the analysis after statistical estimation of wake-group parameters, the retention advantage for emotional material was significantly larger in wake-groups than in sleep-groups (k = 34). Interestingly, however, an additional analysis of k = 8 studies investigating the selective effects of rapid-eye-movement sleep and slow-wave sleep on emotional memory consolidation provided evidence for a selective enhancement of emotional over neutral memory consolidation after rapid-eye-movement sleep compared to slow-wave sleep. These results suggest that sleep does not generally enhance emotional memory consolidation over neutral memory consolidation. However, specific sleep stages might preferentially enhance consolidation of emotional and neutral material, respectively.

neuroscience↗