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Background COVID-19 has introduced novel stressors into American adolescents’ lives. Studies have shown that adolescents adopt an array of coping mechanisms and social supports when contending with stress. It is unclear, though, which strategies are most effective in mitigating daily pandemic-related stress, as few micro-longitudinal studies have explored adolescents’ daily affect during COVID-19. Parental support may also be a critical component of adolescents’ pandemic-related coping, as adolescents’ peer networks have been limited by public health measures. Methods This longitudinal study examined links between stress, coping, parental support, and affect across 14 consecutive days and 6216 assessments from a national sample of adolescents (N=444; Mage=15.0; 60% female; 44% Black/African American, 39% White/Europen American, 9% Latinx, 6% Asian American, 2% Native American) during school closures and state-mandated stay-at-home orders between April 8 and April 21, 2021. Results Adolescents’ health and financial stress predicted increases in same-day (health stress’ effect size = .16; financial stress’ effect size = .11) and next-day negative affect (health stress’ effect size = .05; financial stress’ effect size = .08). Adolescents’ secondary control engagement coping predicted increases in same-day (effect size = .10) and next-day (effect size = .04) positive affect and moderated the link between health stress and negative affect. Parental social support predicted increases in same-day (effect size = .26) and next-day (effect size = .06) positive affect and decreases in same-day (effect size = .17) negative affect and moderated the link between financial stress and negative affect. Limitations Results are indicative of conditions at the immediate onset of COVID-19 and should be interpreted as such. Conclusions Findings provide information as to how health providers and parents can help adolescents mitigate the impact of COVID-19-related health and economic stressors on their psychological well-being. It remains critical to monitor the psychosocial impact of the pandemic on adolescents’ affect while continuing to identify personal and environmental protective factors for reducing harm and maximizing resilience.

Dendritic cells (DC) trigger activation and IFN-γ release by NK cells in lymphoid tissues, a process important for the polarization of Th1 responses. Little is known about the molecular signals that regulate DC-induced NK cell IFN-γ synthesis. In this study, we analyzed whether the interaction between Qa-1b expressed on DC and its CD94/NKG2A receptor on NK cells affects this process. Activation of DC using CpG-oligodeoxynucleotides in Qa-1b-deficient mice, or transfer of CpG-oligodeoxynucleotide-activated Qa-1b-deficient DC into wild-type mice, resulted in dramatically increased IFN-γ production by NK cells, as compared with that induced by Qa-1b-expressing DC. Masking the CD94/NKG2A inhibitory receptor on NK cells in wild-type mice similarly enhanced the IFN-γ response of these cells to Qa-1b-expressing DC. Furthermore, NK cells from CD94/NKG2A-deficient mice displayed higher IFN-γ production upon DC stimulation. These results demonstrate that Qa-1b is critically involved in regulating IFN-γ synthesis by NK cells in vivo through its interaction with CD94/NKG2A inhibitory receptors. This receptor-ligand interaction may be essential to prevent unabated cytokine production by NK cells during an inflammatory response.

Monocytes and T helper (TH) cells rapidly infiltrate inflamed tissues where monocytes differentiate into inflammatory dendritic cells (DCs) through undefined mechanisms. Our studies indicate that TH cells frequently interact with monocytes in inflamed skin and elicit the differentiation of specialized DC subsets characteristic of these lesions. In psoriasis lesions, TH1 and TH17 cells interact with monocytes and instruct these cells to differentiate into TH1- and TH17-promoting DCs, respectively. Correspondingly, in acute atopic dermatitis, TH2 cells interact with monocytes and elicit the formation of TH2-promoting DCs. DC formation requires GM-CSF and cell contact, whereas TH subset specific cytokines dictate DC function and the expression of DC subset specific surface molecules. Moreover, the phenotypes of T cell–induced DC subsets are maintained after subsequent stimulation with a panel of TLR agonists, suggesting that TH-derived signals outweigh downstream TLR signals in their influence on DC function. These findings indicate that TH cells govern the formation and function of specialized DC subsets.

Circulating monocytes can differentiate into dendritic cells (moDCs), which are potent inducers of adaptive immune responses. Previous reports show that granulocyte macrophage–colony-stimulating factor (GM-CSF) and interleukin-4 induce monocyte differentiation into moDCs in vitro, but little is known about the physiological requirements that initiate moDC differentiation in vivo. Here we show that a unique natural killer (NK) cell subset (CD3−CD56bright) that accumulates in lymph nodes and chronically inflamed tissues triggers CD14+ monocytes to differentiate into potent T-helper-1 (TH1) promoting DC. This process requires direct contact of monocytes with NK cells and is mediated by GM-CSF and CD154 derived from NK cells. It is noteworthy that synovial fluid (SF) from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but not osteoarthritis (OA), induces monocytes to differentiate into DC. However, this process occurs only in the presence of NK cells. We propose that NK cells play a role in the maintenance of TH1-mediated inflammatory diseases such as RA by providing a local milieu for monocytes to differentiate into DC.