Human innate lymphoid cells:From helper to killer

Innate Lymphoid Cells (ILCs) control tissue and metabolic homeostasis, but also provide protection from infectious diseases. Strategically located in barrier tissues, ILCs produce effector cytokines in an antigen-independent manner, thereby mounting an appropriate immune response to pathogens at mucosal sites. ILCs are classified into three subsets of helper ILCs, each producing their signature cytokines, and cytotoxic Natural Killer (NK) cells. Their plastic nature allows helper ILC subsets to promptly respond to the changing environment by adapting its function and phenotype. However, when not properly regulated, ILCs can contribute to chronic inflammation, autoimmune disease and cancer. Therefore, it is of importance to identify the essential factors involved in the development and functions of ILCs. In this thesis we describe the methods to isolate ILCs from human mucosal tissues. We identified an essential transcription factor for the development of ILCs by studying the immune cell composition of GATA2-deficient patients. Furthermore, we investigated the full spectrum and the plasticity of human ILCs and NK cells in the tonsil and intestine. Thereby we identified cytotoxic ILCs which are distinct from NK cells and unraveled their developmental requirements. Furthermore, we investigated the ILC composition in the inflamed intestinal tissue of Crohn’s disease patients compared to non-inflamed controls, and observed that particular ILC subsets that express high levels of cytotoxic molecules and type 1 cytokines expanded in inflamed tissues. Our findings contribute to a better understanding of the functions of ILCs and their possible roles in inflammatory diseases of the intestine

Psychosis and urbanicity – a review of the recent literature from epidemiology to neurourbanism

Purpose of review: Epidemiological studies associate city living with an elevated psychosis risk. Urban (social/economic) stress and exposure to environmental toxins, pollution or disease agents have been proposed to underlie this association. This review provides an update on the recent evidence (May 2017 - November 2018). Recent findings: Of 645-screened studies, 17 on: (1) urbanicity-psychosis associations in worldwide high, middle and low-income countries, (2) explanatory mechanisms, including nature exposure, social and economic stressors and genetic risk; (3) urbanicity effects on the brain and coping; and (4) urbanicity and resources, were included. The reviewed evidence revealed complex patterns of urbanicity-psychosis associations with considerable international variation within Europe and between low, middle and high-income countries worldwide. Social and economic stressors (e.g. migration, ethnic density, economic deprivation), nature exposure and access to resources could only explain part of the urbanicity effects. Risk factors differed between countries and between affective and non-affective psychosis. Summary: Urbanicity-psychosis associations are heterogeneous and driven by multiple risk and protective factors that seem to act differently in different ethnic groups and countries. Interdisciplinary research combining approaches, e.g. from experimental neuroscience and epidemiology, is needed to unravel specific urban mechanisms that in- or decrease psychosis risk

Social neuroscience in psychiatry: unravelling the neural mechanisms of social dysfunction

Social neuroscience is a flourishing, interdisciplinary field that investigates the underlying biological processes of social cognition and behaviour. The recent application of social neuroscience to psychiatric research advances our understanding of various psychiatric illnesses that are characterized by impairments in social cognition and social functioning. In addition, the upcoming line of social neuroscience research provides new techniques to design and evaluate treatment interventions that are aimed at improving patients’ social lives. This review provides a contemporary overview of social neuroscience in psychiatry. We draw together the major findings about the neural mechanisms of social cognitive processes directed at understanding others and social interactions in psychiatric illnesses and discuss their implications for future research and clinical practice