Role of the Aryl Hydrocarbon Receptor in Controlling Maintenance and Functional Programs of RORγt+ Innate Lymphoid Cells and Intraepithelial Lymphocytes

Mucosal retinoic receptor-related orphan receptor (ROR)γt-expressing innate lymphoid cells (ILC) play an important role in the defense against intestinal pathogens and in promoting epithelial homeostasis and adaptation, thereby effectively protecting the vertebrate host against intestinal inflammatory disorders. The functional activity of RORγt+ ILC is under the control of environmental cues. However, the molecular sensors for such environmental signals are largely unknown. Recently, the aryl hydrocarbon receptor (AhR) has emerged as a master regulator for the postnatal maintenance of intestinal RORγt+ ILC and intraepithelial lymphocytes. AhR is a highly conserved transcription factor whose activity is regulated by environmental and dietary small molecule ligands. Here, we review the role of AhR signaling for the maintenance of intestinal immune cells and its impact on the immunological protection against intestinal infections and debilitating chronic inflammatory disorders

The Eternal Robot: Anchoring Effects in Humans' Mental Models of Robots and Their Self

Current robot designs often reflect an anthropomorphic approach, apparently aiming to convince users through an ideal system, being most similar or even on par with humans. The present paper challenges human-likeness as a design goal and questions whether simulating human appearance and performance adequately fits into how humans think about robots in a conceptual sense, i.e., human's mental models of robots and their self. Independent of the technical possibilities and limitations, our paper explores robots' attributed potential to become human-like by means of a thought experiment. Four hundred eighty-one participants were confronted with fictional transitions from human-to-robot and robot-to-human, consisting of 20 subsequent steps. In each step, one part or area of the human (e.g., brain, legs) was replaced with robotic parts providing equal functionalities and vice versa. After each step, the participants rated the remaining humanness and remaining self of the depicted entity on a scale from 0 to 100%. It showed that the starting category (e.g., human, robot) serves as an anchor for all former judgments and can hardly be overcome. Even if all body parts had been exchanged, a former robot was not perceived as totally human-like and a former human not as totally robot-like. Moreover, humanness appeared as a more sensible and easier denied attribute than robotness, i.e., after the objectively same transition and exchange of the same parts, the former human was attributed less humanness and self left compared to the former robot's robotness and self left. The participants' qualitative statements about why the robot has not become human-like, often concerned the (unnatural) process of production, or simply argued that no matter how many parts are exchanged, the individual keeps its original entity. Based on such findings, we suggest that instead of designing most human-like robots in order to reach acceptance, it might be more promising to understand robots as an own "species" and underline their specific characteristics and benefits. Limitations of the present study and implications for future HRI research and practice are discussed

Invisible but Understandable: In Search of the Sweet Spot between Technology Invisibility and Transparency in Smart Spaces and Beyond

Smart technology is already present in many areas of everyday life. People rely on algorithms in crucial life domains such as finance and healthcare, and the smart car promises a more relaxed driving experience—all the while, the technology recedes further into the background. The smarter the technology, the more intransparent it tends to become. Users no longer understand how the technology works, what its limits are, and what consequences regarding autonomy and privacy emerge. Both extremes, total invisibility and total transparency, come with specific challenges and do not form reasonable design goals. This research explores the potential tension between smart and invisible versus transparent and understandable technology. We discuss related theories from the fields of explainable AI (XAI) as well as trust psychology, and then introduce transparency in smart spaces as a special field of application. A case study explores specific challenges and design approaches through the example of a so-called room intelligence (RI), i.e., a special kind of smart living room. We conclude with research perspectives for more general design approaches and implications for future research

A murine intestinal intraepithelial NKp46-negative innate lymphoid cell population characterized by group 1 properties

The Ly49E receptor is preferentially expressed on murine innate-like lymphocytes, such as epidermal V gamma 3 T cells, intestinal intraepithelial CD8 alpha alpha(+) T lymphocytes, and CD49a(+) liver natural killer (NK) cells. As the latter have recently been shown to be distinct from conventional NK cells and have innate lymphoid cell type 1 (ILC1) properties, we investigated Ly49E expression on intestinal ILC populations. Here, we show that Ly49E expression is very low on known ILC populations, but it can be used to define a previously unrecognized intraepithelial innate lymphoid population. This Ly49E-positive population is negative for NKp46 and CD8 alpha alpha, expresses CD49a and CD103, and requires T-bet expression and IL-15 signaling for differentiation and/or survival. Transcriptome analysis reveals a group 1 ILC gene profile, different from NK cells, iCD8 alpha cells, and intraepithelial ILC1. Importantly, NKp46(-)CD8 alpha alpha(-)Ly49E(+) cells produce interferon (IFN)-gamma, suggesting that this previously unrecognized population may contribute to Th1-mediated immunity

c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells

RORgt+ group 3 innate lymphoid cells (ILC3s) maintain intestinal homeostasis through secretion of type 3 cytokines such as interleukin (IL)-17 and IL-22. However, CCR6- ILC3s additionally co-express T-bet allowing for the acquisition of type 1 effector functions. While T-bet controls the type 1 programming of ILC3s, the molecular mechanisms governing T-bet are undefined. Here, we identify c-Maf as a crucial negative regulator of murine T-bet+ CCR6- ILC3s. Phenotypic and transcriptomic profiling of c-Maf-deficient CCR6- ILC3s revealed a hyper type 1 differentiation status, characterized by overexpression of ILC1/NK cell-related genes and downregulation of type 3 signature genes. On the molecular level, c-Maf directly restrained T-bet expression. Conversely, c-Maf expression was dependent on T-bet and regulated by IL-1b, IL-18 and Notch signals. Thus, we define c-Maf as a crucial cell-intrinsic brake in the type 1 effector acquisition which forms a negative feedback loop with T-bet to preserve the identity of CCR6-ILC3s

Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19)

Background: Due to the SARS-CoV-2 pandemic, public health interventions have been introduced globally in order to prevent the spread of the virus and avoid the overload of health care systems, especially for the most severely affected patients. Scientific studies to date have focused primarily on describing the clinical course of patients, identifying treatment options and developing vaccines. In Germany, as in many other regions, current tests for SARS-CoV2 are not conducted on a representative basis and in a longitudinal design. Furthermore, knowledge about the immune status of the population is lacking. Nonetheless, these data are needed to understand the dynamics of the pandemic and hence to appropriately design and evaluate interventions. For this purpose, we recently started a prospective population-based cohort in Munich, Germany, with the aim to develop a better understanding of the state and dynamics of the pandemic. Methods: In 100 out of 755 randomly selected constituencies, 3000 Munich households are identified via random route and offered enrollment into the study. All household members are asked to complete a baseline questionnaire and subjects ≥14 years of age are asked to provide a venous blood sample of ≤3 ml for the determination of SARS-CoV-2 IgG/IgA status. The residual plasma and the blood pellet are preserved for later genetic and molecular biological investigations. For twelve months, each household member is asked to keep a diary of daily symptoms, whereabouts and contacts via WebApp. If symptoms suggestive for COVID-19 are reported, family members, including children < 14 years, are offered a pharyngeal swab taken at the Division of Infectious Diseases and Tropical Medicine, LMU University Hospital Munich, for molecular testing for SARS-CoV-2. In case of severe symptoms, participants will be transferred to a Munich hospital. For one year, the study teams re-visits the households for blood sampling every six weeks. Discussion: With the planned study we will establish a reliable epidemiological tool to improve the understanding of the spread of SARS-CoV-2 and to better assess the effectiveness of public health measures as well as their socio-economic effects. This will support policy makers in managing the epidemic based on scientific evidence

Interleukin-12 and -23 Control Plasticity of CD127+ Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria

SummaryHuman group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127+ ILC1, and intraepithelial CD103+ ILC1. In inflamed intestinal tissues from Crohn’s disease patients, numbers of CD127+ ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127+ ILC1 is reversible in vitro and in vivo. CD127+ ILC1 differentiated to ILC3 in the presence of interleukin-2 (IL-2), IL-23, and IL-1β dependent on the transcription factor RORγt, and this process was enhanced in the presence of retinoic acid. Furthermore, we observed in resection specimen from Crohn’s disease patients a higher proportion of CD14+ dendritic cells (DC), which in vitro promoted polarization from ILC3 to CD127+ ILC1. In contrast, CD14− DCs promoted differentiation from CD127+ ILC1 toward ILC3. These observations suggest that environmental cues determine the composition, function, and phenotype of CD127+ ILC1 and ILC3 in the gut