The serine/threonine kinase tumor progression locus 2 (Tpl2, also known as Map3k8/Cot) is a potent inflammatory mediator that drives the production of TNF␣, IL-1␤, and IFN␥. We previously demonstrated that Tpl2 regulates T cell receptor (

Tumor progression locus 2 (Tpl2) is a serine/threonine kinase that regulates the expression of inflammatory mediators in response to Toll-like receptors (TLR) and cytokine receptors. Global ablation of Tpl2 leads to severe disease in response to influenza A virus (IAV) infection, characterized by respiratory distress, and studies in bone marrow chimeric mice implicated Tpl2 in non-hematopoietic cells. Lung epithelial cells are primary targets and replicative niches of influenza viruses; however, the specific regulation of antiviral responses by Tpl2 within lung epithelial cells has not been investigated. Herein, we show that Tpl2 is basally expressed in primary airway epithelial cells and that its expression increases in both type I and type II airway epithelial cells (AECI and AECII) in response to influenza infection. We used Nkx2.1-cre to drive Tpl2 deletion within pulmonary epithelial cells to delineate epithelial cell-specific functions of Tpl2 during influenza infection in mice. Although modest increases in morbidity and mortality were attributed to cre-dependent deletion in lung epithelial cells, no alterations in host cytokine production or lung pathology were observed. In vitro, Tpl2 inhibition within the type I airway epithelial cell line, LET1, as well as genetic ablation in primary airway epithelial cells did not alter cytokine production. Overall, these findings establish that Tpl2-dependent defects in cells other than AECs are primarily responsible for the morbidity and mortality seen in influenza-infected mice with global Tpl2 ablation.

Tamoxifen is commonly used as a cancer treatment in humans and for inducing genetic alterations using Cre-lox mouse models in the research setting. However, the extent of tamoxifen off-target effects in animal research is underappreciated. Here, we report significant changes in cellular infiltration in Cre-recombinase-negative mice treated with tamoxifen intraperitoneally. These changes were noted in the lungs, which were characterized by the presence of alveolitis, vasculitis, and pleuritis. Despite significant immunological changes in response to tamoxifen treatment, clinical symptoms were not observed. This study provides a cautionary note that tamoxifen treatment alone leads to histologic alterations that may obscure research interpretations and further highlights the need for the development of alternative mouse models for inducible Cre-mediated deletion.

Recent societal changes, including a global pandemic, have exacerbated experiences of and attention to burnout related to work and parenting. In the present study, we investigated how several social forces can act as demands and resources to impact work-related and parental burnout. We tested two primary hypotheses in a sample of women who responded to an online survey (N for analyses ranged from 2376 to 3525). We found that social comparisons, social media use, negative emotions when comparing oneself to others on social media, and a high do it all discrepancy (feeling one should be able to do it all more so than perceptions that one can) were correlated with higher reports of work-related and parental burnout. Alternatively, positive emotions when comparing oneself to others and social support were related to lower reports of work-related and parental burnout. The influence of social media use on burnout was mediated by the emotions experienced when comparing oneself to others on social media. Tests of moderation indicated that social comparisons had stronger relationships with burnout for those with higher expectations that they should be able to do it all verses can do it all. Tests of social support as a moderator of the relationships between social demands and burnout were largely non-significant. Based on these findings, we make practical suggestions for interventions to increase positive emotions experienced from social media use, and to mediate the do it all discrepancy by redefining expectations around “doing it all.”