Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS.

The liver is bathed in bacterial products, including lipopolysaccharide transported from the intestinal portal vasculature, but maintains a state of tolerance that is exploited by persistent pathogens and tumours1-4. The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8+ T cells compartmentalized in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins and are enriched in close proximity to CD14high myeloid cells in hepatic zone 2. CD14+CD8+ T cells preferentially accumulate within the donor pool in liver allografts, among hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14+CD8+ T cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10 and IL-2 production ex vivo, and enhanced antiviral/anti-tumour effector function after TCR engagement. This CD14+CD8+ T cell profile can be recapitulated by the acquisition of membrane proteins-including the lipopolysaccharide receptor complex-from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T cells in vitro. CD14+CD8+ T cells express integrins and chemokine receptors that favour interactions with the local stroma, which can promote their induction through CXCL12. Lipopolysaccharide can also increase the frequency of CD14+CD8+ T cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut-liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+ T cells with immunomodulatory ability.

The Relationship Between Climate Change Issue Engagement, Connection to Nature and Mental Wellbeing.

As the threat of climate change becomes increasingly prevalent for people in both the developed and developing world, the impact of climate change on mental wellbeing has become a crucial area of research. In addition to the direct, indirect, and psychosocial impacts of climate change on mental wellbeing, there is also a question of how climate change driven changes to the environment will influence the well-established positive relationship between connection to nature and mental wellbeing. The aim of this study was to investigate the relationship between climate change issue engagement, connection to nature, and mental wellbeing in English speaking adults over 18 years of age. This study examined the average levels of connection to nature and mental wellbeing in people with different levels of climate change issue engagement, and evaluated whether a person's level of climate change issue engagement uniquely predicted mental wellbeing. The study corroborated positive relationships between wellbeing and various aspects of relatedness to nature in the overall sample. The strength of these relationships, however, depended on the level of climate change issue engagement. More specifically, the level of engagement is inversely linked to mental wellbeing, such that the lower the level of engagement, generally the higher is wellbeing.